CN101181388B - Mass control method of keke oral preparation - Google Patents
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- CN101181388B CN101181388B CN2007100780111A CN200710078011A CN101181388B CN 101181388 B CN101181388 B CN 101181388B CN 2007100780111 A CN2007100780111 A CN 2007100780111A CN 200710078011 A CN200710078011 A CN 200710078011A CN 101181388 B CN101181388 B CN 101181388B
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Abstract
The invention provides a quality control method for Keke oral preparation. The quality control method mainly comprises the partial or all the parts of items of character, identification, inspection and content testing, wherein, the identification comprises a microscopical identification, and a thin-layer chromatography identification for medical materials such as ephedra herb, liquoric root and pappy shell; and the content testing comprises the testing on morphine content inside the pappy shell. Compared with the prior art, the invention has the advantages of high precision, good reproducibility, high recycling rate, accurate measuring result, increasing the quality control standard of the Keke oral preparation and effectively controlling the quality of the products, thereby completely ensuring the clinical curing effect and the body health of patients.
Description
Technical field: the present invention relates to a kind of method of quality control of keke oral preparation for relieving cough, belong to technical field of medicaments.
Background technology: cough is a kind of common disease in our daily life, cough stopping formulation is to develop on the Ma Xing Shi Gan Tang basis of China's traditional Chinese medical science famous classic treatise on Febrile Diseases, is total to seven flavor medicine by Chinese ephedra, pappy shell, Radix Glycyrrhizae, semen armeniacae amarae, radish seed, balloonflower root, gypsum and forms; Have the heat-clearing of a surname's lung, cough-relieving, the effect of relievining asthma, to the infection of the upper respiratory tract, tracheitis, pneumonia, diseases such as cough have definite curative effect.Wherein " cough-stopping (Ke Ke) capsule " publication is the 17 of Drug Standard of Ministry of Public Health of the Peoples Republic of China, and this medicine is used for many years clinically, obtains satisfied result of treatment at treatment cough, asthma fermentation.Morphine is not carried out identification check in the existing preparation, because pappy shell is the medicine that plays a major role in the cough stopping formulation, so contained morphine carries out the quality that identification check can be controlled said preparation well in the reply pappy shell.
Summary of the invention:
The objective of the invention is to: the method for quality control that a kind of keke oral preparation for relieving cough is provided.This oral solid formulation comprises capsule, tablet and granule, by method of quality control of the present invention, can effectively control the quality of this keke oral solid preparation for treating cough, to guarantee the clinical efficacy of said preparation.
Keke oral preparation for relieving cough of the present invention is to constitute like this: calculate according to composition by weight: it mainly is prepared from by Chinese ephedra 120-480, pappy shell 120-480, Radix Glycyrrhizae 120-480, semen armeniacae amarae 120-480, radish seed 35-150, balloonflower root 35-150, gypsum 35-150.
Keke oral preparation for relieving cough of the present invention is preparation like this: Chinese ephedra, pappy shell partly are ground into fine powder, and residue Chinese ephedra, pappy shell meal decoct 1-5 time with acidic aqueous solution, collecting decoction filters, and filtrate transfers pH value to 6-8, soup is standby, five tastes boilings such as all the other Radix Glycyrrhizaes 1-5 time, collecting decoction, filter, filtrate and above-mentioned solution merge, and are concentrated into the thick paste shape, add Chinese ephedra and pappy shell fine powder mixing, add auxiliary material again, make capsule, tablet or granule according to the method for routine.
The method of quality control of keke oral preparation for relieving cough of the present invention is like this: it comprises proterties, inspection, discriminating and assay, and described proterties is: for capsule, the product content thing is that pale brown look is to tan powder or particle, mildly bitter flavor; For tablet, medicine shows pale brown look to sepia, mildly bitter flavor; For granule, product is yellow to tan particle; Described inspection is: moisture: should cross 12.0%, other: should meet Chinese Pharmacopoeia about the relevant regulations under capsule, tablet or the granule item; Described discriminating comprises microscopical identification, with the ephedrine hydrochloride reference substance side of discriminating epheday intermedia medicinal material, with licorice medicinal materials in the enoxolone reference substance discriminating side, differentiate with the thin layer of pappy shell medicinal material in morphine reference substance, codeine phosphate reference substance, the papaverine hydrochloride reference substance discriminating side; Described assay comprises the content assaying method to morphine.
The discrimination method of its epheday intermedia is to be contrast with the ephedrine hydrochloride reference substance, and with chloroform: methyl alcohol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is the thin-layered chromatography of developping agent; The discrimination method of Radix Glycyrrhizae is to be contrast with the enoxolone reference substance, and with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is the thin-layered chromatography of developping agent; The discrimination method of pappy shell is to be contrast with morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, and with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is the thin-layered chromatography of developping agent.
Discrimination method comprises the part or all of of following project:
(1) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, put microscopically and observe: the exocarp cell is pentagon or rectangle like, and wall is the beads shape and thickens, and the guard cell side is seen and is dumbbell shaped.
(2) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize adds ammonia solution number droplet, mixes thoroughly, adds chloroform, and cold soaking spends the night, and filters, and filtrate adds watery hydrochloric acid, and jolting divides and gets the sour water layer, and evaporate to dryness, residue add methyl alcohol makes dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance, adds dissolve with methanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methyl alcohol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is a developping agent, launch, take out, dry, spray is with 0.1-1% triketohydrindene hydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(3) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize adds the mixed solution of hydrochloric acid and chloroform, puts reflux in the water-bath, puts coldly, filters, and filtrate evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Extracting liquorice hypo acid reference substance adds dissolve with ethanol, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is a developping agent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(4) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize adds methylene chloride and ammoniacal liquor, and sonicated filters, and filtrate evaporate to dryness, residue add methyl alcohol makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes mixed solution, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is a developping agent, launches, and takes out, dry, put under the uviol lamp and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
Concrete discrimination method comprises the part or all of of following project:
(1) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, put microscopically and observe: the exocarp cell is pentagon or rectangle like, and wall is the beads shape and thickens, and the guard cell side is seen and is dumbbell shaped.
(2) get cough-stopping (Ke Ke) capsule agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 10-50ml, cold soaking spends the night, and filters, and filtrate adds watery hydrochloric acid 1-10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methyl alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 5-25 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methyl alcohol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is a developping agent, launch, take out, dry, spray is with 0.1-1% triketohydrindene hydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating 2-10 minute; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(3) get cough-stopping (Ke Ke) capsule agent, each 2g of tablet respectively, or get granule 20g, porphyrize adds hydrochloric acid 0.5-5ml and chloroform 10-30ml, puts in the water-bath reflux 0.5-3 hour, puts coldly, filters, and filtrate evaporate to dryness, residue add ethanol 1-5ml makes dissolving, as need testing solution; Extracting liquorice hypo acid reference substance adds dissolve with ethanol and makes the solution that every 1ml contains 1-5mg, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 2-20 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is a developping agent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 2-10 minute; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(4) get cough-stopping (Ke Ke) capsule agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds methylene chloride 10-50ml, ammoniacal liquor 0.5-5ml, and sonicated 10-60 minute, filter, filtrate evaporate to dryness, residue add methyl alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw each 2-20 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is a developping agent, launches, and takes out, dry, put under the uviol lamp 200-500nm and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
The content assaying method of morphine is to be contrast with the morphine reference substance in the pappy shell, and with methyl alcohol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is the high performance liquid chromatography of moving phase.
The content assaying method of morphine is: according to Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filling agent; With methyl alcohol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a moving phase; The detection wavelength is 100-600nm; Flow velocity is: 0.5-3ml/min; Number of theoretical plate should be not less than 3000 by the morphine peak;
The preparation of reference substance solution: get the morphine reference substance, the accurate title, decide, and adds dissolve with methanol, promptly;
The preparation of need testing solution: get the preparation of the present invention under the content uniformity item, porphyrize, the accurate title, decide, and puts in the tool plug conical flask, adds methylene chloride, ammoniacal liquor, sonicated; Put coldly, filter, residue filters with washed with dichloromethane 1-5 time, combined dichloromethane liquid, and water-bath volatilizes methylene chloride, and residue adds methyl alcohol makes dissolving, and quantitatively is transferred in the measuring bottle, is diluted to scale with methyl alcohol, shakes up, and the miillpore filter filtration is got subsequent filtrate, promptly;
Determination method: accurate respectively reference substance solution and the need testing solution drawn, inject liquid chromatograph, measure, promptly; In this keke oral preparation for relieving cough, contain pappy shell in the capsule, should be 0.03-3mg/g, contain pappy shell in the tablet, should be 0.01-3mg/g, contain pappy shell in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
The morphine content assay method is more specifically: according to Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filling agent; With methyl alcohol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a moving phase; The detection wavelength is 100-600nm; Flow velocity is: 0.5-3ml/min; Number of theoretical plate should be not less than 3000 by the morphine peak;
The preparation of reference substance solution: get the morphine reference substance, the accurate title, decide, and adds methyl alcohol and make the solution that every 1ml contains 10-100ug, promptly;
The preparation of need testing solution: get the preparation of the present invention under the content uniformity item, porphyrize is got capsule, tablet 0.5g, or get granule 4g, the accurate title, decide, and puts in the 50ml tool plug conical flask, add the 10-50ml methylene chloride, 0.5-5ml ammoniacal liquor, sonicated 10-60 minute; Put coldly, filter, residue is with washed with dichloromethane 1-5 time, filtration, combined dichloromethane liquid, water-bath volatilizes methylene chloride, and residue adds methyl alcohol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methyl alcohol, shake up,, get subsequent filtrate, promptly smaller or equal to the miillpore filter filtration of 0.45 μ m;
Determination method: accurate respectively reference substance solution and each 5-25 μ l of need testing solution of drawing, inject liquid chromatograph, measure, promptly; In this keke oral preparation for relieving cough, contain pappy shell in the capsule, should be 0.03-3mg/g, contain pappy shell in the tablet, should be 0.01-3mg/g, contain pappy shell in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
Method of quality control of the present invention comprises:
Proterties;
For capsule: the product content thing is that pale brown look is to tan powder or particle, mildly bitter flavor;
For tablet: medicine shows pale brown look to sepia, mildly bitter flavor;
For granule: product is yellow to tan particle;
Differentiate:
(1) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, put microscopically and observe: the exocarp cell is pentagon or rectangle like, and wall is the beads shape and thickens, and the guard cell side is seen and is dumbbell shaped.
(2) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize adds ammonia solution number droplet, mixes thoroughly, adds chloroform, and cold soaking spends the night, and filters, and filtrate adds watery hydrochloric acid, and jolting divides and gets the sour water layer, and evaporate to dryness, residue add methyl alcohol makes dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance, adds dissolve with methanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methyl alcohol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is a developping agent, launch, take out, dry, spray is with 0.1-1% triketohydrindene hydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(3) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize adds the mixed solution of hydrochloric acid and chloroform, puts reflux in the water-bath, puts coldly, filters, and filtrate evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Extracting liquorice hypo acid reference substance adds dissolve with ethanol, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is a developping agent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(4) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize adds methylene chloride and ammoniacal liquor, and sonicated filters, and filtrate evaporate to dryness, residue add methyl alcohol makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes mixed solution, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=5 40: 5-40: 1-10: 0.5-5 is a developping agent, launches, and takes out, dry, put under the uviol lamp and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the relevant regulations under capsule, tablet or the granule item;
Assay: according to Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filling agent; With methyl alcohol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a moving phase; The detection wavelength is 100-600nm; Flow velocity is: 0.5-3ml/min; Number of theoretical plate should be not less than 3000 by the morphine peak;
The preparation of reference substance solution: get the morphine reference substance, the accurate title, decide, and adds dissolve with methanol, promptly;
The preparation of need testing solution: get the preparation of the present invention under the content uniformity item, porphyrize, the accurate title, decide, and puts in the tool plug conical flask, adds methylene chloride, ammoniacal liquor, sonicated; Put coldly, filter, residue filters with washed with dichloromethane 1-5 time, combined dichloromethane liquid, and water-bath volatilizes methylene chloride, and residue adds methyl alcohol makes dissolving, and quantitatively is transferred in the measuring bottle, is diluted to scale with methyl alcohol, shakes up, and the miillpore filter filtration is got subsequent filtrate, promptly;
Determination method: accurate respectively reference substance solution and the need testing solution drawn, inject liquid chromatograph, measure, promptly; In this keke oral preparation for relieving cough, contain pappy shell in the capsule, should be 0.03-3mg/g, contain pappy shell in the tablet, should be 0.01-3mg/g, contain pappy shell in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
Concrete method of quality control is:
Proterties;
For capsule: the product content thing is that pale brown look is to tan powder or particle, mildly bitter flavor;
For tablet: medicine shows pale brown look to sepia, mildly bitter flavor;
For granule: product is yellow to tan particle;
Differentiate:
(1) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, put microscopically and observe: the exocarp cell is pentagon or rectangle like, and wall is the beads shape and thickens, and the guard cell side is seen and is dumbbell shaped.
(2) get cough-stopping (Ke Ke) capsule agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 10-50ml, cold soaking spends the night, and filters, and filtrate adds watery hydrochloric acid 1-10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methyl alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 5-25 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methyl alcohol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is a developping agent, launch, take out, dry, spray is with 0.1-1% triketohydrindene hydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating 2-10 minute; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(3) get cough-stopping (Ke Ke) capsule agent, each 2g of tablet respectively, or get granule 20g, porphyrize adds hydrochloric acid 0.5-5ml and chloroform 10-30ml, puts in the water-bath reflux 0.5-3 hour, puts coldly, filters, and filtrate evaporate to dryness, residue add ethanol 1-5ml makes dissolving, as need testing solution; Extracting liquorice hypo acid reference substance adds dissolve with ethanol and makes the solution that every 1ml contains 1-5mg, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 2-20 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is a developping agent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 2-10 minute; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(4) get cough-stopping (Ke Ke) capsule agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds methylene chloride 10-50ml, ammoniacal liquor 0.5-5ml, and sonicated 10-60 minute, filter, filtrate evaporate to dryness, residue add methyl alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw each 2-20 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is a developping agent, launches, and takes out, dry, put under the uviol lamp 200-500nm and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the relevant regulations under capsule, tablet or the granule item;
Assay: according to Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filling agent; With methyl alcohol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a moving phase; The detection wavelength is 100-600nm; Flow velocity is: 0.5-3ml/min; Number of theoretical plate should be not less than 3000 by the morphine peak;
The preparation of reference substance solution: get the morphine reference substance, the accurate title, decide, and adds methyl alcohol and make the solution that every 1ml contains 10-100ug, promptly;
The preparation of need testing solution: get the preparation of the present invention under the content uniformity item, porphyrize is got capsule, tablet 0.5g, or get granule 4g, the accurate title, decide, and puts in the 50ml tool plug conical flask, add the 10-50ml methylene chloride, 0.5-5ml ammoniacal liquor, sonicated 10-60 minute; Put coldly, filter, residue is with washed with dichloromethane 1-5 time, filtration, combined dichloromethane liquid, water-bath volatilizes methylene chloride, and residue adds methyl alcohol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methyl alcohol, shake up,, get subsequent filtrate, promptly smaller or equal to the miillpore filter filtration of 0.45 μ m;
Determination method: accurate respectively reference substance solution and each 5-25 μ l of need testing solution of drawing, inject liquid chromatograph, measure, promptly; In this keke oral preparation for relieving cough, contain pappy shell in the capsule, should be 0.03-3mg/g, contain pappy shell in the tablet, should be 0.01-3mg/g, contain pappy shell in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
Method of quality control of the present invention is the preferred plan that obtains through a large amount of shaker tests, and following experimental study is a preferred process of the present invention:
The Study on Identification of pappy shell medicinal material:
Reference substance: morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance are Nat'l Pharmaceutical ﹠ Biological Products Control Institute and provide.
1, the test sample preparation method selects:
Method one: get this product 5g, add methyl alcohol 30ml, reflux 30 minutes filters while hot, and filtrate evaporate to dryness, residue add methyl alcohol 1ml makes dissolving, as need testing solution; Lack the pappy shell negative controls with the method preparation.。
Method two: get this product 5g, add methylene chloride 30ml and ammoniacal liquor 1ml, ultrasonic 20 minutes, filter, filtrate evaporate to dryness, residue add methyl alcohol 1ml makes dissolving, as need testing solution; Lack the pappy shell negative controls with the method preparation.
Method three: get preparation 5g, add absolute ethyl alcohol 50ml, put in the water-bath reflux 1 hour, filter, filtrate evaporate to dryness, residue add water 50 makes dissolving, transfer PH to 9-10 with strong ammonia solution, filter, filtrate is used chloroform extraction 2 times, each 20ml, the combined chloroform extract, low temperature volatilizes, and residue adds absolute ethyl alcohol 1ml makes dissolving, as need testing solution; Lack the pappy shell negative controls with the method preparation.
Method four: get preparation 5g, add ethyl acetate 40ml and ammoniacal liquor 1ml, sonicated 20 minutes filters, and filtrate evaporate to dryness, residue add methyl alcohol 1ml makes dissolving, as need testing solution; Lack the pappy shell negative controls with the method preparation.
Method five: get preparation 5g, transfer pH9～10 with ammonia solution, extract 2 times with ethyl acetate, each 20ml merges ethyl acetate liquid, and water bath method, residue add methyl alcohol 1ml makes dissolving, as need testing solution; Lack the pappy shell negative controls with the method preparation.
In experimentation, we find, because morphine, codeine phosphate, papaverine hydrochloride all be fat-soluble composition, and the contained flavour of a drug of this product are more, cause the composition that extracts more, need testing solution concentration is too big, puts the thin layer plate difficulty; In experiment, find, extract and effective ingredient can be proposed, and need testing solution is easy to a plate with methylene chloride, negative noiseless simultaneously, so system of selection two prepares need testing solutions.
2, developping agent is selected: the solution with toluene, acetone, ethanol, strong ammonia solution different proportion is developping agent, found that, with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is a developping agent, the exhibition effect is better, and the best is a toluene: acetone: ethanol: strong ammonia solution=20: 20: 3: 1.
3, thin layer plate is selected: 1. the silica gel g thin-layer plate with the preparation of 2% sodium hydroxide solution launches, the result after spray is with developer on morphine and the codeine phosphate relevant position spot very unintelligible.2. launch with silica gel g thin-layer plate, result's each corresponding spot colour developing after spray is with developer is clear, so determine to select for use silica gel g thin-layer plate.
4, developer is selected: be developer with rare bismuth potassium iodide test solution and sodium nitrite ethanol test solution 1., the result shows that this chromogenic reagent is not obvious, will spray trouble of two kinds of developers simultaneously successively.2. be developer with the improvement bismuth potassium iodide test solution, fruit is shown that this chromogenic reagent is obvious, clear, be the improvement bismuth potassium iodide test solution so determine developer.
5, observation condition: put earlier under the uviol lamp (365nm) and inspect, spray with behind the developer again, daylight is observed.Through test of many times, under uviol lamp, can only observe the fluorescence spot of morphine, so determine observation condition be: put under the uviol lamp (365nm) and inspect.In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
Show that through above-mentioned experiment this discrimination method specificity is strong, degree of separation is good, and the spot colour developing is clear, and negative control is noiseless, and the method reappearance is best.
Compared with prior art, method of quality control precision height of the present invention, favorable reproducibility, recovery height, measurement result is accurate, has improved the quality control standard of cough-stopping (Ke Ke) capsule, can control product quality effectively, thereby definitely guarantee the healthy of its clinical efficacy and extensive patients.
Embodiment:
The embodiment of the invention 1:
Proterties;
For capsule: the product content thing is that pale brown look is to tan powder or particle, mildly bitter flavor;
For tablet: medicine shows pale brown look to sepia, mildly bitter flavor;
For granule: product is yellow to tan particle;
Differentiate:
(1) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, put microscopically and observe: the exocarp cell is pentagon or rectangle like, and wall is the beads shape and thickens, and the guard cell side is seen and is dumbbell shaped.
(2) get cough-stopping (Ke Ke) capsule agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 50ml, cold soaking spends the night, and filters, and filtrate adds watery hydrochloric acid 10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methyl alcohol 0.5ml makes dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 3mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 25 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methyl alcohol: strong ammonia solution=5: 0.5: 0.5 is a developping agent, launch, take out, dry, spray is with 1% triketohydrindene hydrate butanol solution: acetic acid=30: 0.5 mixed solutions, 105 ℃ of heating 10 minutes; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(3) get cough-stopping (Ke Ke) capsule agent, each 2g of tablet respectively, or get granule 20g, porphyrize adds hydrochloric acid 5ml and chloroform 30ml, puts in the water-bath reflux 0.5 hour, puts coldly, filters, and filtrate evaporate to dryness, residue add ethanol 5ml makes dissolving, as need testing solution; Extracting liquorice hypo acid reference substance adds dissolve with ethanol and makes the solution that every 1ml contains 5mg, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=5: 10: 15: 1 is developping agent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 2 minutes; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(4) get cough-stopping (Ke Ke) capsule agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds methylene chloride 50ml, ammoniacal liquor 5ml, and sonicated 10 minutes filters, and filtrate evaporate to dryness, residue add methyl alcohol 3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 3mg, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=5: 5: 10: 5 is developping agent, launches, and takes out, dry, put under the uviol lamp 500nm and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the relevant regulations under capsule, tablet or the granule item;
Assay: according to Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filling agent; With methyl alcohol: 1% ammonium acetate aqueous solution: 0.5% triethylamine=50: 100: 0.5 is a moving phase; The detection wavelength is 600nm; Flow velocity is: 3ml/min; Number of theoretical plate should be not less than 3000 by the morphine peak;
The preparation of reference substance solution: get the morphine reference substance, the accurate title, decide, and adds methyl alcohol and make the solution that every 1ml contains 100ug, promptly;
The preparation of need testing solution: get the preparation of the present invention under the content uniformity item, porphyrize is got capsule, tablet 0.5g, or gets granule 4g, and accurate the title decides, and puts in the 50ml tool plug conical flask, adds the 10ml methylene chloride, 0.5ml ammoniacal liquor, sonicated 60 minutes; Put coldly, filter, residue filters combined dichloromethane liquid with washed with dichloromethane 1 time, water-bath volatilizes methylene chloride, and residue adds methyl alcohol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methyl alcohol, shake up, the miillpore filter of 0.1 μ m filters, and gets subsequent filtrate, promptly;
Determination method: accurate respectively reference substance solution and each 5 μ l of need testing solution of drawing, inject liquid chromatograph, measure, promptly; In this keke oral preparation for relieving cough, contain pappy shell in the capsule, should be 0.03-3mg/g, contain pappy shell in the tablet, should be 0.01-3mg/g, contain pappy shell in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
The embodiment of the invention 2:
Proterties;
For capsule: the product content thing is that pale brown look is to tan powder or particle, mildly bitter flavor;
For tablet: medicine shows pale brown look to sepia, mildly bitter flavor;
For granule: product is yellow to tan particle;
Differentiate:
(1) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, put microscopically and observe: the exocarp cell is pentagon or rectangle like, and wall is the beads shape and thickens, and the guard cell side is seen and is dumbbell shaped.
(2) get cough-stopping (Ke Ke) capsule agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 10ml, cold soaking spends the night, and filters, and filtrate adds watery hydrochloric acid 10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methyl alcohol 3ml makes dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methyl alcohol: strong ammonia solution=20: 5: 0.05 is a developping agent, launch, take out, dry, spray is with 0.1% triketohydrindene hydrate butanol solution: acetic acid=10: 5 mixed solutions, 105 ℃ of heating 2 minutes; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(3) get cough-stopping (Ke Ke) capsule agent, each 2g of tablet respectively, or get granule 20g, porphyrize adds hydrochloric acid 0.5ml and chloroform 10ml, puts in the water-bath reflux 3 hours, puts coldly, filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Extracting liquorice hypo acid reference substance adds dissolve with ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 20 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=25: 30: 2: 0.1 is developping agent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 10 minutes; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(4) get cough-stopping (Ke Ke) capsule agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds methylene chloride 10ml, ammoniacal liquor 0.5ml, and sonicated 60 minutes filters, and filtrate evaporate to dryness, residue add methyl alcohol 0.5ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw each 20 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=40: 40: 1: 0.5 is developping agent, launches, and takes out, dry, put under the uviol lamp 200nm and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the relevant regulations under capsule, tablet or the granule item;
Assay: according to Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filling agent; With methyl alcohol: 0.1% ammonium acetate aqueous solution: 5% triethylamine=10: 50: 5 is a moving phase; The detection wavelength is 100nm; Flow velocity is: 0.5ml/min; Number of theoretical plate should be not less than 3000 by the morphine peak;
The preparation of reference substance solution: get the morphine reference substance, the accurate title, decide, and adds methyl alcohol and make the solution that every 1ml contains 10ug, promptly;
The preparation of need testing solution: get the preparation of the present invention under the content uniformity item, porphyrize is got capsule, tablet 0.5g, or gets granule 4g, and accurate the title decides, and puts in the 50ml tool plug conical flask, adds the 50ml methylene chloride, 5ml ammoniacal liquor, sonicated 10 minutes; Put coldly, filter, residue filters combined dichloromethane liquid with washed with dichloromethane 5 times, water-bath volatilizes methylene chloride, and residue adds methyl alcohol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methyl alcohol, shake up, the miillpore filter of 0.25 μ m filters, and gets subsequent filtrate, promptly;
Determination method: accurate respectively reference substance solution and each 25 μ l of need testing solution of drawing, inject liquid chromatograph, measure, promptly; In this keke oral preparation for relieving cough, contain pappy shell in the capsule, should be 0.03-3mg/g, contain pappy shell in the tablet, should be 0.01-3mg/g, contain pappy shell in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
The embodiment of the invention 3:
Proterties;
For capsule: the product content thing is that pale brown look is to tan powder or particle, mildly bitter flavor;
For tablet: medicine shows pale brown look to sepia, mildly bitter flavor;
For granule: product is yellow to tan particle;
Differentiate:
(1) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, put microscopically and observe: the exocarp cell is pentagon or rectangle like, and wall is the beads shape and thickens, and the guard cell side is seen and is dumbbell shaped.
(2) get cough-stopping (Ke Ke) capsule agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 20ml, cold soaking spends the night, and filters, and filtrate adds watery hydrochloric acid 5ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methyl alcohol 1ml makes dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 2mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methyl alcohol: strong ammonia solution=10: 2: 0.1 is a developping agent, launch, take out, dry, spray is with 0.3% triketohydrindene hydrate butanol solution: acetic acid=19: 1 mixed solutions, 105 ℃ of heating 5 minutes; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(3) get cough-stopping (Ke Ke) capsule agent, each 2g of tablet respectively, or get granule 20g, porphyrize adds hydrochloric acid 1ml and chloroform 20ml, puts in the water-bath reflux 1 hour, puts coldly, filters, and filtrate evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Extracting liquorice hypo acid reference substance adds dissolve with ethanol and makes the solution that every 1ml contains 2mg, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 4 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=10: 20: 7: 0.5 is developping agent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 5 minutes; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
(4) get cough-stopping (Ke Ke) capsule agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds methylene chloride 30ml, ammoniacal liquor 1ml, and sonicated 20 minutes filters, and filtrate evaporate to dryness, residue add methyl alcohol 1ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=20: 20: 3: 1 is developping agent, launches, and takes out, dry, put under the uviol lamp 365nm and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the relevant regulations under capsule, tablet or the granule item;
Assay: according to Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filling agent; With methyl alcohol: 0.5% ammonium acetate aqueous solution: 1% triethylamine=25: 74: 1 is a moving phase; The detection wavelength is 215nm; Flow velocity is: 1.0ml/min; Number of theoretical plate should be not less than 3000 by the morphine peak;
The preparation of reference substance solution: get the morphine reference substance, the accurate title, decide, and adds methyl alcohol and make the solution that every 1ml contains 40ug, promptly;
The preparation of need testing solution: get the preparation of the present invention under the content uniformity item, porphyrize is got capsule, tablet 0.5g, or gets granule 4g, and accurate the title decides, and puts in the 50ml tool plug conical flask, adds the 30ml methylene chloride, 1ml ammoniacal liquor, sonicated 30 minutes; Put coldly, filter, residue filters combined dichloromethane liquid with washed with dichloromethane 3 times, water-bath volatilizes methylene chloride, and residue adds methyl alcohol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methyl alcohol, shake up, the miillpore filter of 0.45 μ m filters, and gets subsequent filtrate, promptly;
Determination method: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject liquid chromatograph, measure, promptly; In this keke oral preparation for relieving cough, contain pappy shell in the capsule, should be 0.03-3mg/g, contain pappy shell in the tablet, should be 0.01-3mg/g, contain pappy shell in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
Claims (4)
1. the detection method of a keke oral preparation for relieving cough, this oral formulations comprises capsule, tablet and granule, and described detection method comprises proterties, inspection, discriminating and assay, and described proterties is: for capsule, the product content thing is that pale brown look is to tan powder or particle, mildly bitter flavor; For tablet, medicine shows pale brown look to sepia, mildly bitter flavor; For granule, product is yellow to tan particle; Described inspection is: moisture: should cross 12.0%, other: should meet Chinese Pharmacopoeia about the relevant regulations under capsule, tablet or the granule item; Described discriminating comprises microscopical identification, with the ephedrine hydrochloride reference substance side of discriminating epheday intermedia medicinal material, with licorice medicinal materials in the enoxolone reference substance discriminating side, differentiate with the thin layer of pappy shell medicinal material in morphine reference substance, codeine phosphate reference substance, the papaverine hydrochloride reference substance discriminating side; Described assay comprises the content assaying method to morphine, it is characterized in that: the discrimination method of pappy shell medicinal material is: get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize, add methylene chloride 10-50ml, ammoniacal liquor 0.5-5ml, sonicated, filter, filtrate evaporate to dryness, residue add methyl alcohol makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes mixed solution, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is a developping agent, launches, and takes out, dry, put under the uviol lamp and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
2. the detection method of keke oral preparation for relieving cough according to claim 1, it is characterized in that: the discrimination method of pappy shell medicinal material is: get cough-stopping (Ke Ke) capsule agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds methylene chloride 10-50ml, ammoniacal liquor 0.5-5ml, sonicated 10-60 minute, filter the filtrate evaporate to dryness, residue adds methyl alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw each 2-20 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is a developping agent, launches, and takes out, dry, put under the uviol lamp 200-500nm and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.
3. the quality inspection survey method of keke oral preparation for relieving cough according to claim 1, it is characterized in that: described detection method is:
Proterties;
For capsule: the product content thing is that pale brown look is to tan powder or particle, mildly bitter flavor;
For tablet: medicine shows pale brown look to sepia, mildly bitter flavor;
For granule: product is yellow to tan particle;
Differentiate:
(1) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, put microscopically and observe: the exocarp cell is pentagon or rectangle like, and wall is the beads shape and thickens, and the guard cell side is seen and is dumbbell shaped;
(2) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize adds ammonia solution number droplet, mixes thoroughly, adds chloroform, and cold soaking spends the night, and filters, and filtrate adds watery hydrochloric acid, and jolting divides and gets the sour water layer, and evaporate to dryness, residue add methyl alcohol makes dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance, adds dissolve with methanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methyl alcohol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is a developping agent, launch, take out, dry, spray is with 0.1-1% triketohydrindene hydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;
(3) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize adds the mixed solution of hydrochloric acid and chloroform, puts reflux in the water-bath, puts coldly, filters, and filtrate evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Extracting liquorice hypo acid reference substance adds dissolve with ethanol, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is a developping agent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;
(4) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, porphyrize adds methylene chloride 10-50ml, ammoniacal liquor 0.5-5ml, and sonicated filters, and filtrate evaporate to dryness, residue add methyl alcohol makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes mixed solution, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is a developping agent, launches, and takes out, dry, put under the uviol lamp and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the relevant regulations under capsule, tablet or the granule item;
Assay: according to Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filling agent; With methyl alcohol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a moving phase; The detection wavelength is 100-600nm; Flow velocity is: 0.5-3ml/min; Number of theoretical plate should be not less than 3000 by the morphine peak;
The preparation of reference substance solution: get the morphine reference substance, the accurate title, decide, and adds dissolve with methanol, promptly;
The preparation of need testing solution: get the preparation of the present invention under the content uniformity item, porphyrize, the accurate title, decide, and puts in the tool plug conical flask, adds methylene chloride, ammoniacal liquor, sonicated; Put coldly, filter, residue filters with washed with dichloromethane 1-5 time, combined dichloromethane liquid, and water-bath volatilizes methylene chloride, and residue adds methyl alcohol makes dissolving, and quantitatively is transferred in the measuring bottle, is diluted to scale with methyl alcohol, shakes up, and the miillpore filter filtration is got subsequent filtrate, promptly;
Determination method: accurate respectively reference substance solution and the need testing solution drawn, inject liquid chromatograph, measure, promptly; In this keke oral preparation for relieving cough, contain pappy shell in the capsule, should be 0.03-3mg/g, contain pappy shell in the tablet, should be 0.01-3mg/g, contain pappy shell in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
4. the detection method of keke oral preparation for relieving cough according to claim 1, it is characterized in that: concrete detection method is:
Proterties;
For capsule: the product content thing is that pale brown look is to tan powder or particle, mildly bitter flavor;
For tablet: medicine shows pale brown look to sepia, mildly bitter flavor;
For granule: product is yellow to tan particle;
Differentiate:
(1) get cough-stopping (Ke Ke) capsule agent, tablet or granule respectively, put microscopically and observe: the exocarp cell is pentagon or rectangle like, and wall is the beads shape and thickens, and the guard cell side is seen and is dumbbell shaped;
(2) get cough-stopping (Ke Ke) capsule agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 10-50ml, cold soaking spends the night, and filters, and filtrate adds watery hydrochloric acid 1-10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methyl alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw each 5-25 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methyl alcohol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is a developping agent, launch, take out, dry, spray is with 0.1-1% triketohydrindene hydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating 2-10 minute; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;
(3) get cough-stopping (Ke Ke) capsule agent, each 2g of tablet respectively, or get granule 20g, porphyrize adds hydrochloric acid 0.5-5ml and chloroform 10-30ml, puts in the water-bath reflux 0.5-3 hour, puts coldly, filters, and filtrate evaporate to dryness, residue add ethanol 1-5ml makes dissolving, as need testing solution; Extracting liquorice hypo acid reference substance adds dissolve with ethanol and makes the solution that every 1ml contains 1-5mg, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin-layered chromatography, draw above-mentioned each 2-20 μ 1 of two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of sherwood oils: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is a developping agent, launch, take out, dry, spray is with 10% phosphorus aluminic acid ethanolic solution, 105 ℃ of heating 2-10 minute; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;
(4) get cough-stopping (Ke Ke) capsule agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds methylene chloride 10-50ml, ammoniacal liquor 0.5-5ml, and sonicated 10-60 minute, filter, filtrate evaporate to dryness, residue add methyl alcohol 0.5-3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverine hydrochloride reference substance, adds dissolve with methanol and makes the solution that every 1ml contains 0.5-3mg, in contrast product solution; According to the test of Chinese Pharmacopoeia thin-layered chromatography, draw each 2-20 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is a developping agent, launches, and takes out, dry, put under the uviol lamp 200-500nm and inspect; In the test sample chromatogram, with the corresponding position of morphine reference substance chromatogram on, show the fluorescence spot of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the relevant regulations under capsule, tablet or the granule item;
Assay: according to Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring;
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filling agent; With methyl alcohol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a moving phase; The detection wavelength is 100-600nm; Flow velocity is: 0.5-3ml/min; Number of theoretical plate should be not less than 3000 by the morphine peak;
The preparation of reference substance solution: get the morphine reference substance, the accurate title, decide, and adds methyl alcohol and make the solution that every 1ml contains 10-100ug, promptly;
The preparation of need testing solution: get the preparation of the present invention under the content uniformity item, porphyrize is got capsule, tablet 0.5g, or get granule 4g, the accurate title, decide, and puts in the 50ml tool plug conical flask, add the 10-50ml methylene chloride, 0.5-5ml ammoniacal liquor, sonicated 10-60 minute; Put coldly, filter, residue is with washed with dichloromethane 1-5 time, filtration, combined dichloromethane liquid, water-bath volatilizes methylene chloride, and residue adds methyl alcohol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methyl alcohol, shake up,, get subsequent filtrate, promptly smaller or equal to the miillpore filter filtration of 0.45 μ m;
Determination method: accurate respectively reference substance solution and each 5-25 μ l of need testing solution of drawing, inject liquid chromatograph, measure, promptly; In this keke oral preparation for relieving cough, contain pappy shell in the capsule, should be 0.03-3mg/g, contain pappy shell in the tablet, should be 0.01-3mg/g, contain pappy shell in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
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| CN2007100780111A CN101181388B (en) | 2007-11-19 | 2007-11-19 | Mass control method of keke oral preparation |
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| CN101890095B (en) * | 2009-05-21 | 2012-09-05 | 中山市恒生药业有限公司 | Method for detecting cough tablets |
| CN102914498A (en) * | 2012-10-15 | 2013-02-06 | 辽源誉隆亚东药业有限责任公司 | Yanling Changchun capsule detection method |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1813972A (en) * | 2005-11-25 | 2006-08-09 | 贵州益佰制药股份有限公司 | Method for controlling quality of keke oral solid preparation for treating cough |
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| CN1813972A (en) * | 2005-11-25 | 2006-08-09 | 贵州益佰制药股份有限公司 | Method for controlling quality of keke oral solid preparation for treating cough |
Non-Patent Citations (2)
| Title |
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| 国家药典委员会.中华人民共和国药典一部 2005版.化学工业出版社,2005,256. |
| 国家药典委员会.中华人民共和国药典一部 2005版.化学工业出版社,2005,256. * |
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