CN101181388A - Mass control method of keke oral preparation - Google Patents
Mass control method of keke oral preparation Download PDFInfo
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- CN101181388A CN101181388A CNA2007100780111A CN200710078011A CN101181388A CN 101181388 A CN101181388 A CN 101181388A CN A2007100780111 A CNA2007100780111 A CN A2007100780111A CN 200710078011 A CN200710078011 A CN 200710078011A CN 101181388 A CN101181388 A CN 101181388A
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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 KOUFU ZHIJI, belong to technical field of medicaments.
Background technology: cough is a kind of commonly encountered diseases in our daily life, cough stopping formulation is to develop on the MAXINGSHIGAN TANG basis of China's traditional Chinese medical science famous classic treatise on Febrile Diseases, is total to seven flavor medicine by Herba Ephedrae, Pericarpium Papaveris, Radix Glycyrrhizae, Semen Armeniacae Amarum, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum and forms; Have the lung qi dispersing heat clearing away, cough-relieving, the effect of relievining asthma, to upper respiratory tract infection, tracheitis, pneumonia, diseases such as cough have definite curative effect.Wherein " KEKE JIAONANG " 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 therapeutic effect at treatment cough, asthma fermentation.Morphine is not carried out identification check in the existing preparation, because Pericarpium Papaveris 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 Pericarpium Papaveris.
Summary of the invention:
The objective of the invention is to: the method for quality control that a kind of KEKE KOUFU ZHIJI 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 KOUFU GUTI ZHIJI, to guarantee the clinical efficacy of said preparation.
KEKE KOUFU ZHIJI of the present invention is to constitute like this: calculate according to composition by weight: it mainly is prepared from by Herba Ephedrae 120-480, Pericarpium Papaveris 120-480, Radix Glycyrrhizae 120-480, Semen Armeniacae Amarum 120-480, Semen Raphani 35-150, Radix Platycodonis 35-150, Gypsum Fibrosum 35-150.
KEKE KOUFU ZHIJI of the present invention is preparation like this: Herba Ephedrae, Pericarpium Papaveris partly are ground into fine powder, and residue Herba Ephedrae, Pericarpium Papaveris coarse powder decoct 1-5 time with acidic aqueous solution, collecting decoction filters, and filtrate transfers pH value to 6-8, medicinal liquid is standby, and the five tastes such as all the other Radix Glycyrrhizaes decoct with water collecting decoction 1-5 time, filter, filtrate and above-mentioned solution merge, and are concentrated into the thick paste shape, add Herba Ephedrae and Pericarpium Papaveris fine powder mixing, add adjuvant again, make capsule, tablet or granule according to the method for routine.
The method of quality control of KEKE KOUFU ZHIJI of the present invention is like this: it comprises character, inspection, discriminating and assay, and described character is: for capsule, the product content thing is that pale brown color is to tan powder or granule, mildly bitter flavor; For tablet, medicine shows pale brown color to sepia, mildly bitter flavor; For granule, product is yellow to tan granule; Described inspection is: moisture: should cross 12.0%, other: should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item; Described discriminating comprises microscopical identification, with the ephedrine hydrochloride reference substance side of discriminating epheday intermedia medical material, with licorice medicinal materials in the enoxolone reference substance discriminating side, differentiate with the thin layer of Pericarpium Papaveris medical material in morphine reference substance, codeine phosphate reference substance, the papaverin 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: methanol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is the thin layer chromatography of developing solvent; The discrimination method of Radix Glycyrrhizae is to be contrast with the enoxolone reference substance, and with 30～60 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is the thin layer chromatography of developing solvent; The discrimination method of Pericarpium Papaveris is to be contrast with morphine reference substance, codeine phosphate reference substance, papaverin hydrochloride reference substance, and with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is the thin layer chromatography of developing solvent.
Discrimination method comprises the part or all of of following project:
(1) get KEKE JIAONANG agent, tablet or granule respectively, put microscopically and observe: the outer peel 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 KEKE JIAONANG agent, tablet or granule respectively, porphyrize adds ammonia solution number droplet, mixes thoroughly, adds chloroform, and merceration spends the night, and filters, and filtrate adds dilute hydrochloric acid, and jolting divides and gets the sour water layer, and evaporate to dryness, residue add methanol 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 layer chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methanol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is developing solvent, launch, take out, dry, spray is with 0.1-1% 1,2,3-indantrione monohydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get KEKE JIAONANG 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 subacid reference substance adds dissolve with ethanol, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is developing solvent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get KEKE JIAONANG agent, tablet or granule respectively, porphyrize adds dichloromethane and ammonia, and supersound process filters, and filtrate evaporate to dryness, residue add methanol makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin hydrochloride reference substance, adds dissolve with methanol and makes mixed solution, in contrast product solution; According to the test of Chinese Pharmacopoeia thin layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Concrete discrimination method comprises the part or all of of following project:
(1) get KEKE JIAONANG agent, tablet or granule respectively, put microscopically and observe: the outer peel 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 KEKE JIAONANG agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 10-50ml, merceration spends the night, and filters, and filtrate adds dilute hydrochloric acid 1-10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methanol 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 layer 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: methanol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is developing solvent, launch, take out, dry, spray is with 0.1-1% 1,2,3-indantrione monohydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating 2-10 minute; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get KEKE JIAONANG 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 subacid 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 layer 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 petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is developing solvent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 2-10 minute; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get KEKE JIAONANG agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds dichloromethane 10-50ml, ammonia 0.5-5ml, and supersound process 10-60 minute, filter, filtrate evaporate to dryness, residue add methanol 0.5-3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin 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 layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp 200-500nm and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
The content assaying method of morphine is to be contrast with the morphine reference substance in the Pericarpium Papaveris, and with methanol: 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 mobile 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 filler; With methanol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a mobile 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 dichloromethane, ammonia, supersound process; Put coldly, filter, residue filters with washed with dichloromethane 1-5 time, combined dichloromethane liquid, and water-bath volatilizes dichloromethane, and residue adds methanol makes dissolving, and quantitatively is transferred in the measuring bottle, is diluted to scale with methanol, shakes up, and the microporous filter membrane filtration is got subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance solution and the need testing solution drawn, inject chromatograph of liquid, measure, promptly; In this KEKE KOUFU ZHIJI, contain Pericarpium Papaveris in the capsule, should be 0.03-3mg/g, contain Pericarpium Papaveris in the tablet, should be 0.01-3mg/g, contain Pericarpium Papaveris 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 filler; With methanol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a mobile 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 methanol 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 dichloromethane, 0.5-5ml ammonia, supersound process 10-60 minute; Put coldly, filter, residue is with washed with dichloromethane 1-5 time, filtration, combined dichloromethane liquid, water-bath volatilizes dichloromethane, and residue adds methanol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methanol, shake up,, get subsequent filtrate, promptly smaller or equal to the microporous filter membrane filtration of 0.45 μ m;
Algoscopy: accurate respectively reference substance solution and each 5-25 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; In this KEKE KOUFU ZHIJI, contain Pericarpium Papaveris in the capsule, should be 0.03-3mg/g, contain Pericarpium Papaveris in the tablet, should be 0.01-3mg/g, contain Pericarpium Papaveris in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
Method of quality control of the present invention comprises:
Character;
For capsule: the product content thing is that pale brown color is to tan powder or granule, mildly bitter flavor;
For tablet: medicine shows pale brown color to sepia, mildly bitter flavor;
For granule: product is yellow to tan granule;
Differentiate:
(1) get KEKE JIAONANG agent, tablet or granule respectively, put microscopically and observe: the outer peel 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 KEKE JIAONANG agent, tablet or granule respectively, porphyrize adds ammonia solution number droplet, mixes thoroughly, adds chloroform, and merceration spends the night, and filters, and filtrate adds dilute hydrochloric acid, and jolting divides and gets the sour water layer, and evaporate to dryness, residue add methanol 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 layer chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methanol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is developing solvent, launch, take out, dry, spray is with 0.1-1% 1,2,3-indantrione monohydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get KEKE JIAONANG 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 subacid reference substance adds dissolve with ethanol, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is developing solvent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get KEKE JIAONANG agent, tablet or granule respectively, porphyrize adds dichloromethane and ammonia, and supersound process filters, and filtrate evaporate to dryness, residue add methanol makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin hydrochloride reference substance, adds dissolve with methanol and makes mixed solution, in contrast product solution; According to the test of Chinese Pharmacopoeia thin layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the pertinent 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 filler; With methanol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a mobile 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 dichloromethane, ammonia, supersound process; Put coldly, filter, residue filters with washed with dichloromethane 1-5 time, combined dichloromethane liquid, and water-bath volatilizes dichloromethane, and residue adds methanol makes dissolving, and quantitatively is transferred in the measuring bottle, is diluted to scale with methanol, shakes up, and the microporous filter membrane filtration is got subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance solution and the need testing solution drawn, inject chromatograph of liquid, measure, promptly; In this KEKE KOUFU ZHIJI, contain Pericarpium Papaveris in the capsule, should be 0.03-3mg/g, contain Pericarpium Papaveris in the tablet, should be 0.01-3mg/g, contain Pericarpium Papaveris in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
Concrete method of quality control is:
Character;
For capsule: the product content thing is that pale brown color is to tan powder or granule, mildly bitter flavor;
For tablet: medicine shows pale brown color to sepia, mildly bitter flavor;
For granule: product is yellow to tan granule;
Differentiate:
(1) get KEKE JIAONANG agent, tablet or granule respectively, put microscopically and observe: the outer peel 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 KEKE JIAONANG agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 10-50ml, merceration spends the night, and filters, and filtrate adds dilute hydrochloric acid 1-10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methanol 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 layer 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: methanol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is developing solvent, launch, take out, dry, spray is with 0.1-1% 1,2,3-indantrione monohydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating 2-10 minute; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get KEKE JIAONANG 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 subacid 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 layer 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 petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is developing solvent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 2-10 minute; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get KEKE JIAONANG agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds dichloromethane 10-50ml, ammonia 0.5-5ml, and supersound process 10-60 minute, filter, filtrate evaporate to dryness, residue add methanol 0.5-3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin 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 layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp 200-500nm and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the pertinent 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 filler; With methanol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a mobile 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 methanol 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 dichloromethane, 0.5-5ml ammonia, supersound process 10-60 minute; Put coldly, filter, residue is with washed with dichloromethane 1-5 time, filtration, combined dichloromethane liquid, water-bath volatilizes dichloromethane, and residue adds methanol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methanol, shake up,, get subsequent filtrate, promptly smaller or equal to the microporous filter membrane filtration of 0.45 μ m;
Algoscopy: accurate respectively reference substance solution and each 5-25 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; In this KEKE KOUFU ZHIJI, contain Pericarpium Papaveris in the capsule, should be 0.03-3mg/g, contain Pericarpium Papaveris in the tablet, should be 0.01-3mg/g, contain Pericarpium Papaveris 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 screening tests, and following experimentation is a preferred process of the present invention:
The Study on Identification of Pericarpium Papaveris medical material:
Reference substance: morphine reference substance, codeine phosphate reference substance, papaverin hydrochloride reference substance are Nat'l Pharmaceutical ﹠ Biological Products Control Institute and provide.
1, the test sample preparation method is selected:
Method one: get this product 5g, add methanol 30ml, reflux 30 minutes filters while hot, and filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Lack the Pericarpium Papaveris negative controls with the method preparation.。
Method two: get this product 5g, add methylene chloride 30ml and ammonia 1ml, ultrasonic 20 minutes, filter, filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Lack the Pericarpium Papaveris negative controls with the method preparation.
Method three: get preparation 5g, add dehydrated 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 extracting solution, low temperature volatilizes, and residue adds dehydrated alcohol 1ml makes dissolving, as need testing solution; Lack the Pericarpium Papaveris negative controls with the method preparation.
Method four: get preparation 5g, add ethyl acetate 40ml and ammonia 1ml, supersound process 20 minutes filters, and filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Lack the Pericarpium Papaveris negative controls with the method preparation.
Method five: get preparation 5g, transfer pH9～10 with ammonia solution, use ethyl acetate extraction 2 times, each 20ml merges ethyl acetate liquid, and water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Lack the Pericarpium Papaveris negative controls with the method preparation.
In experimentation, we find, because morphine, codeine phosphate, papaverin 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 lamellae difficulty; In experiment, find, extract and active ingredient can be proposed, and need testing solution is easy to a plate with dichloromethane, negative noiseless simultaneously, so system of selection two prepares need testing solutions.
2, developing solvent is selected: the solution with toluene, acetone, ethanol, strong ammonia solution different proportion is developing solvent, found that, with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is developing solvent, the exhibition effect is better, and the best is a toluene: acetone: ethanol: strong ammonia solution=20: 20: 3: 1.
3, lamellae 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 speckle very unintelligible.2. launch with silica gel g thin-layer plate, result's each corresponding speckle 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 speckle of morphine, so determine observation condition be: put under the uviol lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Show that through above-mentioned experiment this discrimination method specificity is strong, separating degree is good, and the speckle colour developing is clear, and negative control is noiseless, and the method repeatability is best.
Compared with prior art, method of quality control precision height of the present invention, favorable reproducibility, response rate height, measurement result is accurate, has improved the quality control standard of KEKE JIAONANG, can control product quality effectively, thereby definitely guarantee the healthy of its clinical efficacy and extensive patients.
The specific embodiment:
The embodiment of the invention 1:
Character;
For capsule: the product content thing is that pale brown color is to tan powder or granule, mildly bitter flavor;
For tablet: medicine shows pale brown color to sepia, mildly bitter flavor;
For granule: product is yellow to tan granule;
Differentiate:
(1) get KEKE JIAONANG agent, tablet or granule respectively, put microscopically and observe: the outer peel 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 KEKE JIAONANG agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 50ml, merceration spends the night, and filters, and filtrate adds dilute hydrochloric acid 10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methanol 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 layer 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: methanol: strong ammonia solution=5: 0.5: 0.5 is developing solvent, launch, take out, dry, spray is with 1% 1,2,3-indantrione monohydrate butanol solution: acetic acid=30: 0.5 mixed solutions, 105 ℃ of heating 10 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get KEKE JIAONANG 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 subacid 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 layer 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 petroleum ether: benzene: ethyl acetate: glacial acetic acid=5: 10: 15: 1 is developing solvent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 2 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get KEKE JIAONANG agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds dichloromethane 50ml, ammonia 5ml, and supersound process 10 minutes filters, and filtrate evaporate to dryness, residue add methanol 3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin 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 layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp 500nm and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the pertinent 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 filler; With methanol: 1% ammonium acetate aqueous solution: 0.5% triethylamine=50: 100: 0.5 is a mobile 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 methanol 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 dichloromethane, 0.5ml ammonia, supersound process 60 minutes; Put coldly, filter, residue filters combined dichloromethane liquid with washed with dichloromethane 1 time, water-bath volatilizes dichloromethane, and residue adds methanol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methanol, shake up, the microporous filter membrane of 0.1 μ m filters, and gets subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance solution and each 5 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; In this KEKE KOUFU ZHIJI, contain Pericarpium Papaveris in the capsule, should be 0.03-3mg/g, contain Pericarpium Papaveris in the tablet, should be 0.01-3mg/g, contain Pericarpium Papaveris in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
The embodiment of the invention 2:
Character;
For capsule: the product content thing is that pale brown color is to tan powder or granule, mildly bitter flavor;
For tablet: medicine shows pale brown color to sepia, mildly bitter flavor;
For granule: product is yellow to tan granule;
Differentiate:
(1) get KEKE JIAONANG agent, tablet or granule respectively, put microscopically and observe: the outer peel 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 KEKE JIAONANG agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 10ml, merceration spends the night, and filters, and filtrate adds dilute hydrochloric acid 10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methanol 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 layer 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: methanol: strong ammonia solution=20: 5: 0.05 is developing solvent, launch, take out, dry, spray is with 0.1% 1,2,3-indantrione monohydrate butanol solution: acetic acid=10: 5 mixed solutions, 105 ℃ of heating 2 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get KEKE JIAONANG 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 subacid 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 layer 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 petroleum ether: benzene: ethyl acetate: glacial acetic acid=25: 30: 2: 0.1 is developing solvent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 10 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get KEKE JIAONANG agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds dichloromethane 10ml, ammonia 0.5ml, and supersound process 60 minutes filters, and filtrate evaporate to dryness, residue add methanol 0.5ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin 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 layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp 200nm and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the pertinent 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 filler; With methanol: 0.1% ammonium acetate aqueous solution: 5% triethylamine=10: 50: 5 is a mobile 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 methanol 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 dichloromethane, 5ml ammonia, supersound process 10 minutes; Put coldly, filter, residue filters combined dichloromethane liquid with washed with dichloromethane 5 times, water-bath volatilizes dichloromethane, and residue adds methanol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methanol, shake up, the microporous filter membrane of 0.25 μ m filters, and gets subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance solution and each 25 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; In this KEKE KOUFU ZHIJI, contain Pericarpium Papaveris in the capsule, should be 0.03-3mg/g, contain Pericarpium Papaveris in the tablet, should be 0.01-3mg/g, contain Pericarpium Papaveris in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
The embodiment of the invention 3:
Character;
For capsule: the product content thing is that pale brown color is to tan powder or granule, mildly bitter flavor;
For tablet: medicine shows pale brown color to sepia, mildly bitter flavor;
For granule: product is yellow to tan granule;
Differentiate:
(1) get KEKE JIAONANG agent, tablet or granule respectively, put microscopically and observe: the outer peel 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 KEKE JIAONANG agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 20ml, merceration spends the night, and filters, and filtrate adds dilute hydrochloric acid 5ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methanol 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 layer 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: methanol: strong ammonia solution=10: 2: 0.1 is developing solvent, launch, take out, dry, spray is with 0.3% 1,2,3-indantrione monohydrate butanol solution: acetic acid=19: 1 mixed solutions, 105 ℃ of heating 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get KEKE JIAONANG 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 subacid 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 layer 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 petroleum ether: benzene: ethyl acetate: glacial acetic acid=10: 20: 7: 0.5 is developing solvent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get KEKE JIAONANG agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds dichloromethane 30ml, ammonia 1ml, and supersound process 20 minutes filters, and filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin 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 layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp 365nm and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the pertinent 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 filler; With methanol: 0.5% ammonium acetate aqueous solution: 1% triethylamine=25: 74: 1 is a mobile 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 methanol 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 dichloromethane, 1ml ammonia, supersound process 30 minutes; Put coldly, filter, residue filters combined dichloromethane liquid with washed with dichloromethane 3 times, water-bath volatilizes dichloromethane, and residue adds methanol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methanol, shake up, the microporous filter membrane of 0.45 μ m filters, and gets subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; In this KEKE KOUFU ZHIJI, contain Pericarpium Papaveris in the capsule, should be 0.03-3mg/g, contain Pericarpium Papaveris in the tablet, should be 0.01-3mg/g, contain Pericarpium Papaveris in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
Claims (5)
1. the method for quality control of a KEKE KOUFU ZHIJI, this oral formulations comprises capsule, tablet and granule, it is characterized in that: it comprises character, inspection, discriminating and assay, described character is: for capsule, the product content thing is that pale brown color is to tan powder or granule, mildly bitter flavor; For tablet, medicine shows pale brown color to sepia, mildly bitter flavor; For granule, product is yellow to tan granule; Described inspection is: moisture: should cross 12.0%, other: should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item; Described discriminating comprises microscopical identification, with the ephedrine hydrochloride reference substance side of discriminating epheday intermedia medical material, with licorice medicinal materials in the enoxolone reference substance discriminating side, differentiate with the thin layer of Pericarpium Papaveris medical material in morphine reference substance, codeine phosphate reference substance, the papaverin hydrochloride reference substance discriminating side; Described assay comprises the content assaying method to morphine.
2. the method for quality control of KEKE KOUFU ZHIJI according to claim 1, it is characterized in that: the discrimination method of Pericarpium Papaveris is to be contrast with morphine reference substance, codeine phosphate reference substance, papaverin hydrochloride reference substance, and with toluene: acetone: ethanol: strong ammonia solution=5-40: 5-40: 1-10: 0.5-5 is the thin layer chromatography of developing solvent.
3. the method for quality control of KEKE KOUFU ZHIJI according to claim 1 is characterized in that: get KEKE JIAONANG agent, tablet or granule respectively, porphyrize, add dichloromethane and ammonia, supersound process filters, filtrate evaporate to dryness, residue add methanol makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin hydrochloride reference substance, adds dissolve with methanol and makes mixed solution, in contrast product solution; According to the test of Chinese Pharmacopoeia thin layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
4. the method for quality control of KEKE KOUFU ZHIJI according to claim 1, it is characterized in that: get KEKE JIAONANG agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds dichloromethane 10-50ml, ammonia 0.5-5ml, supersound process 10-60 minute, filter the filtrate evaporate to dryness, residue adds methanol 0.5-3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin 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 layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp 200-500nm and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
5. the method for quality control of KEKE KOUFU ZHIJI according to claim 1, it is characterized in that: method of quality control of the present invention comprises:
Character;
For capsule: the product content thing is that pale brown color is to tan powder or granule, mildly bitter flavor;
For tablet: medicine shows pale brown color to sepia, mildly bitter flavor;
For granule: product is yellow to tan granule;
Differentiate:
(1) get KEKE JIAONANG agent, tablet or granule respectively, put microscopically and observe: the outer peel 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 KEKE JIAONANG agent, tablet or granule respectively, porphyrize adds ammonia solution number droplet, mixes thoroughly, adds chloroform, and merceration spends the night, and filters, and filtrate adds dilute hydrochloric acid, and jolting divides and gets the sour water layer, and evaporate to dryness, residue add methanol 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 layer chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform: methanol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is developing solvent, launch, take out, dry, spray is with 0.1-1% 1,2,3-indantrione monohydrate butanol solution: acetic acid=10-30: 0.5 5 mixed solutions, 105 ℃ of heating; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(3) get KEKE JIAONANG 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 subacid reference substance adds dissolve with ethanol, in contrast product solution in addition; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 30～60 ℃ of petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is developing solvent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(4) get KEKE JIAONANG agent, tablet or granule respectively, porphyrize adds dichloromethane and ammonia, and supersound process filters, and filtrate evaporate to dryness, residue add methanol makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin hydrochloride reference substance, adds dissolve with methanol and makes mixed solution, in contrast product solution; According to the test of Chinese Pharmacopoeia thin layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the pertinent 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 filler; With methanol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a mobile 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 dichloromethane, ammonia, supersound process; Put coldly, filter, residue filters with washed with dichloromethane 1-5 time, combined dichloromethane liquid, and water-bath volatilizes dichloromethane, and residue adds methanol makes dissolving, and quantitatively is transferred in the measuring bottle, is diluted to scale with methanol, shakes up, and the microporous filter membrane filtration is got subsequent filtrate, promptly;
Algoscopy: accurate respectively reference substance solution and the need testing solution drawn, inject chromatograph of liquid, measure, promptly; In this KEKE KOUFU ZHIJI, contain Pericarpium Papaveris in the capsule, should be 0.03-3mg/g, contain Pericarpium Papaveris in the tablet, should be 0.01-3mg/g, contain Pericarpium Papaveris in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
6, the method for quality control of KEKE KOUFU ZHIJI according to claim 1, it is characterized in that: concrete method of quality control is:
Character;
For capsule: the product content thing is that pale brown color is to tan powder or granule, mildly bitter flavor;
For tablet: medicine shows pale brown color to sepia, mildly bitter flavor;
For granule: product is yellow to tan granule;
Differentiate:
(1) get KEKE JIAONANG agent, tablet or granule respectively, put microscopically and observe: the outer peel 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 KEKE JIAONANG agent, each 3g of tablet respectively, or get granule 20g, porphyrize adds ammonia solution number droplet, mixes thoroughly, add chloroform 10-50ml, merceration spends the night, and filters, and filtrate adds dilute hydrochloric acid 1-10ml, jolting, divide and get the sour water layer, evaporate to dryness, residue add methanol 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 layer 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: methanol: strong ammonia solution=5-20: 0.5-5: 0.05-0.5 is developing solvent, launch, take out, dry, spray is with 0.1-1% 1,2,3-indantrione monohydrate butanol solution: acetic acid=10-30: the 0.5-5 mixed solution, 105 ℃ of heating 2-10 minute; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(3) get KEKE JIAONANG 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 subacid 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 layer 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 petroleum ether: benzene: ethyl acetate: glacial acetic acid=5-25: 10-30: 2-15: 0.1-1 is developing solvent, launch, take out, dry, spray is with 10% phosphomolybdic acid ethanol solution, 105 ℃ of heating 2-10 minute; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(4) get KEKE JIAONANG agent, each 5g of tablet respectively, or get granule 40g, porphyrize adds dichloromethane 10-50ml, ammonia 0.5-5ml, and supersound process 10-60 minute, filter, filtrate evaporate to dryness, residue add methanol 0.5-3ml makes dissolving, as need testing solution; Other gets morphine reference substance, codeine phosphate reference substance, papaverin 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 layer 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 developing solvent, launches, and takes out, dry, put under the uviol lamp 200-500nm and inspect; In the test sample chromatograph, with the corresponding position of morphine reference substance chromatograph on, show the fluorescence speckle of same color; Spray again with the improvement bismuth potassium iodide test solution, put under the daylight and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
Check:
Moisture: should cross 12.0%;
Other: should meet Chinese Pharmacopoeia about the pertinent 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 filler; With methanol: the 0.1-1% ammonium acetate aqueous solution: 0.5-5% triethylamine=10-50: 50-100: 0.5-5 is a mobile 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 methanol 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 dichloromethane, 0.5-5ml ammonia, supersound process 10-60 minute; Put coldly, filter, residue is with washed with dichloromethane 1-5 time, filtration, combined dichloromethane liquid, water-bath volatilizes dichloromethane, and residue adds methanol makes dissolving, and quantitatively is transferred in the 5ml measuring bottle, is diluted to scale with methanol, shake up,, get subsequent filtrate, promptly smaller or equal to the microporous filter membrane filtration of 0.45 μ m;
Algoscopy: accurate respectively reference substance solution and each 5-25 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; In this KEKE KOUFU ZHIJI, contain Pericarpium Papaveris in the capsule, should be 0.03-3mg/g, contain Pericarpium Papaveris in the tablet, should be 0.01-3mg/g, contain Pericarpium Papaveris in the granule, should be 0.001-1mg/g in morphine in morphine in morphine.
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| CN101181388B CN101181388B (en) | 2010-12-15 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100510743C (en) * | 2005-11-25 | 2009-07-08 | 贵州益佰制药股份有限公司 | Method for detecting keke oral solid preparation for treating cough |
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2007
- 2007-11-19 CN CN2007100780111A patent/CN101181388B/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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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| CN101181388B (en) | 2010-12-15 |
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