CN110018254A - A kind of quality determining method of metho kahuangmin oral administration solution - Google Patents

A kind of quality determining method of metho kahuangmin oral administration solution Download PDF

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CN110018254A
CN110018254A CN201910324681.XA CN201910324681A CN110018254A CN 110018254 A CN110018254 A CN 110018254A CN 201910324681 A CN201910324681 A CN 201910324681A CN 110018254 A CN110018254 A CN 110018254A
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solution
reference substance
oral administration
water
diluted
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刘均正
谭闽怀
童猛辉
陈有兵
聂水金
廖园红
刘仙辉
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Jiangxi Heying Pharmaceuticals Co Ltd
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Jiangxi Heying Pharmaceuticals Co Ltd
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/74—Optical detectors

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  • General Health & Medical Sciences (AREA)
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  • Spectroscopy & Molecular Physics (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention discloses a kind of quality determining method of metho kahuangmin oral administration solution, which includes: to p-aminophenol, to chlorobenzene acetamide, calculus bovis factitius and in relation to the identification of substance.The quality determining method of metho kahuangmin oral administration solution provided by the invention can simultaneously detect 15 kinds of compounds; it is effectively increased control of the metho kahuangmin oral administration solution in relation to substance and calculus bovis factitius, so that metho kahuangmin oral administration solution Product Safety and validity have obtained better control；Cannot be to detecting in metho kahuangmin oral administration solution in relation to substance and calculus bovis factitius content in existing method the problem of is also overcomed simultaneously.

Description

A kind of quality determining method of metho kahuangmin oral administration solution
Technical field
The invention belongs to pharmaceutical fields, are related to a kind of quality determining method of extract oral solution, more particularly to one kind The quality determining method of metho kahuangmin oral administration solution.
Background technique
Metho kahuangmin oral administration solution is mainly used for fever, headache, nasal obstruction, pharyngalgia caused by alleviating children's cold or influenza etc. Symptom.
[composition] prescription (1): every 1ml 12.5mg containing paracetamol, caffeine 0.75mg, chlorphenamine maleate 0.15mg, calculus bovis factitius 0.5mg；
Prescription (2): every 1ml 25mg containing paracetamol, caffeine 1.5mg, chlorphenamine maleate 0.3mg, manually Cow-bezoar 1mg
[character] is faint yellow or light brown clear liquid, sweet, slight bitter have refrigerant sense.
[usage and dosage] prescription (1): take orally 1~4 years old children, one time 0.5；5~9 years old children, one time 1；10 years old with 1.5-2 branch of upper children.3 times a day；
Prescription (2): it is oral, 3 times a day.2-3 years old one time 1/2；4-6 years old one time 2/3；7-9 years old one time 1；10 years old With last 1.5-2 branch.
[adverse reaction] has slight dizzy, out of strength, nauseous, epigastric discomfort, dry, anorexia and fash etc. sometimes, can Voluntarily restore.
[taboo] serious hepatic and kidney function obstacle person disabling.
[points for attention] 1. medication 3-7 days, symptom is not alleviated, asks Ref Dr or pharmacist；2. must not during taking this product It drinks or containing spirituous beverage；3. other similar with this product composition cannot be taken simultaneously to resist.
[pharmacological action] paracetamol is prostaglandin synthase inhibitor, has antipyretic effect；Caffeine For central stimulant, the amplitude that can be shunk the cerebrovascular, mitigate its beating can increase the antipyretic-antalgic effect of paracetamol； Chlorphenamine maleate is antihistamine, can mitigate the symptoms such as runny nose, sneezing caused by catching a cold；Calculus bovis factitius has antipyretic Relieving convulsion effect.Compound is made in above-mentioned all medicines, with antipyretic, analgesia, the work for releasing or improving various symptoms caused by flu or influenza With.
The prescription of metho kahuangmin oral administration solution mainly by, caffeine, chlorphenamine maleate, calculus bovis factitius and other Material composition, in order to preferably control the quality of product, improves the safety of drug since contained bulk pharmaceutical chemicals ingredient is more The characteristics of property, the present invention is according to primary raw material medicine, formulate the identification method of drug and the test method of active constituent content.
Summary of the invention
In view of this, the main purpose of the present invention is to provide a kind of quality determining method of metho kahuangmin oral administration solution, Solving existing detection method cannot ask in relation to what substance and calculus bovis factitius content were detected in metho kahuangmin oral administration solution Topic.
In order to achieve the above objectives, the technical scheme of the present invention is realized as follows: a kind of matter of metho kahuangmin oral administration solution Quantity measuring method, the detection method include: to p-aminophenol, to chlorobenzene acetamide and in relation to the identification of substance, specific identification side Method is as follows:
1) preparation of test solution: taking this product prescription, 1. 2. appropriate, this product prescription is placed in measuring bottle, adds the first methanol-water Solution is diluted to scale, as test solution；
2) preparation of reference substance solution: p-aminophenol reference substance, precision title appropriate to chlorobenzene acetamide reference substance are taken respectively It is fixed, add the second methanol aqueous solution to dissolve, is made respectively containing p-aminophenol, to the solution of chlorobenzene acetamide, as reference substance solution；
3) preparation of contrast solution: accurate measurement first reference substance solution and the test solution are set same respectively In measuring bottle, it is diluted to scale with second methanol aqueous solution, is shaken up, as contrast solution；
4) high performance liquid chromatography Mass Spectrometer Method: being filler with octadecylsilane chemically bonded silica；With phosphate solution For mobile phase A, using methanol as Mobile phase B, according to the form below carries out gradient elution；Detection wavelength is 200~250nm；Column temperature be 20~ 45℃；Number of theoretical plate is calculated by paracetamol peak is not less than 2000, p-aminophenol, to chlorobenzene acetamide and acetparaminosalol The separating degree at phenol peak should meet the requirements；Precision measures contrast solution and each 20 μ l of test solution, is injected separately into liquid chromatograph Detection.
Preferably, specific step is as follows for the step 1): taking that this product prescription is 1. appropriate, 2. 5ml is placed in this product prescription 10ml measuring bottle, adding the volume ratio of methanol and water is (4~5): the methanol aqueous solution of (5~6) is diluted to scale, molten as test sample Liquid.
Preferably, specific step is as follows for the step 2): taking p-aminophenol reference substance respectively, compares to chlorobenzene acetamide Appropriate product, accurately weighed, adding the volume ratio of the methanol and water is (4~5): the methanol aqueous solution dissolution of (5~6) is made every In lml respectively containing 0.01~0.2mg of p-aminophenol~, to 0.01~0.2mg of chlorobenzene acetamide~solution, it is molten as reference substance Liquid；
Preferably, specific step is as follows for the step 3): precision measures first reference substance solution and described for examination Each 1ml of product solution is set in same 100ml measuring bottle, and be (4~5) with the volume ratio of the methanol and water: the methanol of (5~6) is water-soluble Liquid is diluted to scale, shakes up, as contrast solution；
Preferably, in the step 4), phosphate is by potassium dihydrogen phosphate and dipotassium hydrogen phosphate group in the phosphate solution At or sodium dihydrogen phosphate and disodium hydrogen phosphate composition, and select water as solvent preparation solution, the pH of the phosphate solution is 5.8~8.0.
Preferably, in the step 4), Parameters of gradient elution are as follows:
Preferably, detection method further include: the identification to calculus bovis factitius, specific identification method are as follows:
1) preparation of cholic acid reference substance solution: taking cholic acid reference substance 12.5mg, accurately weighed, sets in 25ml measuring bottle, adds 50 ~70% glacial acetic acid solution makes to dissolve, and is diluted to scale, shakes up, and cholic acid reference substance solution is made；
2) preparation of standard curve: precision measures cholic acid reference substance solution 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1ml, point It is not placed in tool plug test tube, each pipe is added 50~70% glacial acetic acid solutions and is diluted to 1.0ml, then adds the furfuryl aldehyde solution of brand-new respectively (1 → 100) 1.0ml, shakes up, and 4~6min is placed in ice bath, and precision is added sulfuric acid solution and (takes sulfuric acid 50ml and water 65ml mixed Close) 13ml, it mixes, heats 10min in 70 DEG C of water-baths, move in ice bath, place 2 minutes, using corresponding reagent as blank；
3) UV-VIS spectrophotometry detects: measuring absorbance at the wavelength of 600~610nm, is vertical with absorbance Coordinate, concentration are abscissa, are detected；
4) accurate to measure this product prescription 1. 100ml, prescription 2. 50ml, it sets in separatory funnel, is saturated with water n-butanol and extracts 4 Secondary, each 25ml, combined extract, water bath method, residue adds 60% glacial acetic acid to dissolve and is diluted in 25ml measuring bottle, shake up, Filtration, discards primary filtrate, and precision measures each 1ml of subsequent filtrate, set in two tool plug test tubes of first, second respectively, in first Guan Zhongjia brand-new Furfuryl aldehyde solution 1ml, second Guan Jiashui 1ml makees blank, the method under sighting target directrix curve preparation, from " placing 5min in ice bath " Rise, measure absorbance in accordance with the law, from standard curve read test solution in the weight containing cholic acid, calculate to get
Compared with prior art, the quality determining method of metho kahuangmin oral administration solution provided by the invention can be simultaneously to 15 Kind compound is detected, and control of the metho kahuangmin oral administration solution in relation to substance and calculus bovis factitius is effectively increased, so that ammonia The yellow quick oral administration solution Product Safety of coffee and validity have obtained better control；Also overcoming simultaneously cannot be right in existing method The problem of being detected in metho kahuangmin oral administration solution in relation to substance and calculus bovis factitius content.
Detailed description of the invention
Fig. 1 is solvent blank HPLC chromatogram；
Fig. 2 is cholic acid reference substance solution spectral scan figure；
Fig. 3 is metho kahuangmin oral solution (prescription (1)) test solution spectral scan figure；
Fig. 4 is metho kahuangmin oral solution (prescription (2)) test solution spectral scan figure；
Fig. 5 is to lack calculus bovis factitius feminine gender solution spectrum scanning figure；
Fig. 6 is blank spectral scan figure；
Fig. 7 is cholic acid linear relationship chart.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to the accompanying drawings and embodiments, right The present invention is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, and It is not used in the restriction present invention.
A kind of quality determining method of metho kahuangmin oral administration solution provided in this embodiment, which includes: to right Amino phenols, to chlorobenzene acetamide and in relation to the identification of substance:
The sample message of above-mentioned metho kahuangmin oral administration solution is as follows:
P-aminophenol, to chlorobenzene acetamide and the specific identification method in relation to substance is as follows:
1 test material
1.1 reference substance
Paracetamol (lot number: 100018-201610), p-aminophenol (impurity K, lot number: 100802-201604), To chlorobenzene acetamide (impurity J, lot number: 100850-201803), provided by National Institute for Food and Drugs Control.
Paracetamol impurity A (lot number: A158490), paracetamol impurity C (lot number: A168175), to second Acylamino- phenol impurity E (lot number: H739980), paracetamol impurity F (lot number: N496945), paracetamol impurity H (lot number: A161215), paracetamol impurity I (lot number: H739970) is provided by TRC., Canada.
Paracetamol impurity B (lot number: C4X-12111, content 99.6%), paracetamol impurity D (lot number: C4X-12115, content 99.9%), paracetamol impurity G (lot number: C4X-12118, content 99.9%), acetparaminosalol Phenol impurity L (lot number: C4X-12116, content 98.6%), paracetamol impurity M (lot number: C4X-12114, content 97.2%), paracetamol impurity N (lot number: C4X-12115, content 99.9%), by CATOResearchChemicalsInc. it provides.
1.2 reagents: the reagents such as potassium dihydrogen phosphate, dipotassium hydrogen phosphate, 10% tetrabutylammonium hydroxide, phosphoric acid are analysis It is pure；Methanol is chromatographically pure；Water is purified water.
2 p-aminophenols verify the qualitative of chlorobenzene acetamide, method for quantitatively determining
The preparation of 2.1 solution
1) preparation of test solution: taking that this product prescription is 1. appropriate, 2. 5ml is placed in 10ml measuring bottle to this product prescription, adds methanol The methanol aqueous solution that volume ratio with water is 4:6 is diluted to scale, as test solution；
2) preparation of reference substance solution: p-aminophenol reference substance, precision title appropriate to chlorobenzene acetamide reference substance are taken respectively It is fixed, add the methanol aqueous solution that the volume ratio of methanol and water is 4:6 to dissolve, be made in every lml respectively 0.lmg containing p-aminophenol, to chlorine The solution of phenyl acetamide 0.lmg, as reference substance solution；
3) preparation of contrast solution: precision measures first reference substance solution and each 1ml of the test solution, sets same In one 100ml measuring bottle, the methanol aqueous solution that the volume ratio with the methanol and water is 4:6 is diluted to scale, shakes up, as control Solution；
4) preparation in relation to substance (impurity) reference substance solution: take respectively related substance A, B, C, D, E, F, G, H, I, J, K, L, M, N reference substance are appropriate, and single impurity reference substance solution of every lml containing 0.lmg is made in solubilizer；
5) it lacks the preparation of paracetamol feminine gender solution: taking scarce paracetamol negative sample appropriate, as scarce pair Paracetamol feminine gender solution.
The selection of 2.2 Detection wavelengths
Using Agilent DAD detector, to paracetamol, p-aminophenol, exist to chlorobenzene acetamide reference substance solution Spectral scan is carried out at 200~400nm wavelength, paracetamol and p-aminophenol have maximum suction at 245nm as the result is shown It receives, also has absorption at 245nm wavelength to chlorobenzene acetamide, therefore select 245nm
2.3 high performance liquid chromatography Mass Spectrometer Methods
It is filler with octadecylsilane chemically bonded silica；(potassium dihydrogen phosphate 1.7g, dipotassium hydrogen phosphate are taken with phosphate 1.8g, being dissolved in water to 1000ml) is mobile phase A, and using methanol as Mobile phase B, according to the form below 1 carries out gradient elution；Detection wavelength For 245nm；Column temperature is 40 DEG C；Number of theoretical plate is calculated by paracetamol peak is not less than 2000, p-aminophenol, to chlorobenzene acetyl The separating degree of amine and paracetamol peak should meet the requirements；Precision measures contrast solution and each 20 μ l of test solution, respectively Liquid chromatograph detection is injected, record chromatographic data (see Table 2 for details~table 20 and Fig. 1): when liquid chromatograph detects, test sample In solution chromatogram if any with p-aminophenol, to the consistent chromatographic peak of chlorobenzene acetamide retention time, must not mistake containing p-aminophenol The 0.1% of paracetamol labelled amount, containing the 0.1% of paracetamol labelled amount must not be crossed to chlorobenzene acetamide；If any Other impurity peaks, chromatographic peak (auxiliary material and maleic acid), opposite guarantor except opposite paracetamol peak retention time less than 0.35 Stay the time be about 0.65 (auxiliary material), about 2.48 (caffeines) chromatographic peak disregard outer, other single impurity peak areas must not be big 0.1 times (0.1%) of paracetamol peak area, the sum of other each impurity peak areas are not greater than control in contrast solution 1 times (1.0%) of paracetamol peak area in solution.
1 gradient elution data of table
2 contrast solution HPLC chromatogram data of table
3 prescription of table (2) (lot number 20170716) test solution HPLC chromatogram data
4 prescription of table (2) (lot number 20170707) test solution HPLC chromatogram data e4
5 prescription of table (1) (lot number 20170708) test solution HPLC chromatogram data
6 prescription of table (1) (lot number 20170711) test solution HPLC chromatogram data
Table 7 impurity K (p-aminophenol) reference substance solution HPLC chromatogram data
Table 8 impurity J (to chlorobenzene acetamide) reference substance solution HPLC chromatogram data
9 impurity A reference substance solution HPLC chromatogram of table
10 impurity B reference substance solution HPLC chromatogram data of table
11 impurity C reference substance solution HPLC chromatogram data of table
12 impurity D reference substance solution HPLC chromatogram data of table
13 impurity E reference substance solution HPLC chromatogram data of table
14 impurity F reference substance solution HPLC chromatogram data of table
15 impurity G reference substance solution HPLC chromatogram data of table
16 impurity H reference substance solution HPLC chromatogram data of table
17 impurity I reference substance solution HPLC chromatogram data of table
18 impurity L reference substance solution HPLC chromatogram data of table
19 impurity M reference substance solution HPLC chromatogram data of table
20 impurity N reference substance solution HPLC chromatogram data of table
Table 21 lacks paracetamol feminine gender Solution H PLC chromatographic data
It can be shown that from table 2- table 21 and Fig. 1, p-aminophenol and paracetamol separating degree are 21, to chlorobenzene acetyl Amine and paracetamol separating degree are 100, and number of theoretical plate is calculated by paracetamol peak is not less than 2000, are met the requirements. The peak sequence of impurity peaks be impurity K (p-aminophenol) > impurity B > impurity A > impurity C > impurity F > impurity E > impurity M > impurity D > Impurity G > impurity H > impurity L > impurity N > impurity J (to chlorobenzene acetamide) > impurity I；It can reach between each impurity and efficiently separate, It is noiseless to lack paracetamol feminine gender.
2.4 p-aminophenols carry out quantitative detection to chlorobenzene acetamide and related substance:
Pass through the retention time at each peak in analytical table 2- table 21 and peak area out, it is known that, this product prescription 1. sample with The concrete content of the prescription 2. related substance of control sample is as shown in table 22 below:
22 metho kahuangmin oral administration solution Related substances separation result (%) of table
The embodiment of the invention also includes the identification to more calculus bovis factitiuses, specific identification method is as follows:
1 test material
1.1 reference substances: cholic acid (lot number: grind purchased from Chinese food drug assay by 100078-201415, content 98.9% Study carefully institute).
1.2 reagents: the reagents such as n-butanol, glacial acetic acid, furfural, sulfuric acid are that analysis is pure；Water is purified water.
1.3 instruments: 2655 type ultraviolet specrophotometer of Shimadzu, ten a ten thousandth electronic analytical balance of METTLERTOLEDO.
The verifying of 2 calculus bovis factitius content assaying methods
The preparation of 2.1 solution
The preparation of reference substance solution: taking cholic acid reference substance 12.5mg, accurately weighed, sets in 25ml measuring bottle, adds 60% ice vinegar Acid solution makes to dissolve, and is diluted to scale, shakes up to get (containing cholic acid 0.5mg) in every 1ml.
The preparation of test solution: precision measures this product (prescription (1)) 100ml, (prescription (2)) 50ml, sets separatory funnel In, be saturated with water n-butanol extract 4 times, each 25ml, combined extract, water bath method, residue add 60% glacial acetic acid dissolution simultaneously It is diluted in 25ml measuring bottle, shakes up, as test solution.
The preparation for lacking calculus bovis factitius feminine gender solution takes scarce calculus bovis factitius negative sample 100ml, according to " the system of test solution It is standby " the obtained scarce calculus bovis factitius feminine gender solution of method.
2.2 chromogenic reaction
The preparation precision of standard curve measures reference substance solution 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1.0ml, sets respectively In tool plug test tube, each pipe is added 60% glacial acetic acid solution and is diluted to 1.0ml, then adds the furfuryl aldehyde solution (1 → 100) of brand-new respectively 1.0ml shakes up, and places 5 minutes in ice bath, and sulfuric acid solution (sulfuric acid 50ml is taken to mix with water 65ml) 13ml is added in precision, mixes It is even, heat 10min in 70 DEG C of water-baths, move in ice bath rapidly, place 2 minutes, using corresponding reagent as blank, according to it is ultraviolet- Visible spectrophotometry (general rule 0401) measures absorbance at the wavelength of 605nm, and using absorbance as ordinate, concentration is horizontal seat Mark draws standard curve.
Measuring method precision measures this product prescription 1. 100ml, prescription 2. 50ml, sets in separatory funnel, is saturated with water n-butanol It extracting 4 times, each 25ml, combined extract, water bath method, residue adds 60% glacial acetic acid to dissolve and is diluted in 25ml measuring bottle, It shakes up, filters, discard primary filtrate, precision measures each 1ml of subsequent filtrate, set in two tool plug test tubes of first, second respectively, in first Guan Zhongjia The furfuryl aldehyde solution 1ml of brand-new, second Guan Jiashui 1ml make blank, and the method under sighting target directrix curve preparation " places 5 certainly in ice bath Minute " rise, measure absorbance in accordance with the law, from standard curve read test solution in the weight containing cholic acid, calculate to get.
The selection of 2.3 Detection wavelengths
Precision measures reference substance solution 0.6ml, sets in tool plug test tube, and 60% glacial acetic acid solution is added and is diluted to 1.0ml, then Respectively plus the furfuryl aldehyde solution of brand-new (1 → 100) 1.0ml, it shakes up, is placed 5 minutes in ice bath, precision is added sulfuric acid solution and (takes Sulfuric acid 50ml is mixed with water 65ml) 13ml, it mixes, heats 10 minutes in 70 DEG C of water-baths, move in ice bath rapidly, place 2min, using corresponding reagent as blank, scanning optical spectrum figure, the result is shown in Figure 1 in 500~700nm wave-length coverage；The result shows that most Big absorbing wavelength is 605nm, therefore is selected as Detection wavelength.
The test of 2.4 specificities
Reference substance solution is taken respectively, test solution, lacks calculus bovis factitius feminine gender solution and blank, in 500~700nm wavelength Uv absorption spectra is measured in range, as a result sees Fig. 2~6.
2.5 linear relationships are investigated
Precision measure concentration be cholic acid reference substance solution 0.2ml, 0.4ml of 0.5083mg/ml, 0.6ml, 0.8ml, 1.0ml is set in tool plug test tube respectively, and each pipe is added 60% glacial acetic acid solution and is diluted to 1.0ml, then adds the furfural of brand-new molten respectively Liquid (1 → 100) 1.0ml, shakes up, and places 5 minutes in ice bath, and precision is added sulfuric acid solution and (takes sulfuric acid 50ml and water 65ml mixed Close) 13ml, it mixes, heats 10min in 70 DEG C of water-baths, move in ice bath rapidly, place 2nin, be sky with corresponding reagent It is white, according to UV-VIS spectrophotometry, absorbance is measured at the wavelength of 605nm, using absorbance as ordinate, concentration is cross Coordinate draws standard curve.Obtain regression equation are as follows: y=1.2816x-0.0007, R2=0.9994, the range of linearity is 0.1017mg/ml~0.5083mg/ml.It the results are shown in Table 23 and Fig. 7.
23 linear relationship of table investigates result
The result shows that: linear relationship is good within the scope of 0.1017mg/ml~0.5083mg/ml.
2.6 precision test
Cholic acid reference substance solution is taken, METHOD FOR CONTINUOUS DETERMINATION 6 times, absorbance is recorded, the results are shown in Table 24.
24 Precision test result of table
The result shows that: this law precision is good.
2.7 solution stability testing
Reference substance solution, test solution are taken respectively, was measured at 0,5,15,30,45,60 minute, record absorbance, as a result It is shown in Table 25.
25 solution stability testing result of table
The result shows that: reference substance solution and test solution are stablized in 60 minutes.
2.8 repetitive test
Each 6 parts of metho kahuangmin oral administration solution sample of lot number 20170708,20170707 batches are taken respectively, are measured in accordance with the law, are counted Content is calculated, the results are shown in Table 26.
26 repetitive test result of table
The result shows that: this law repeatability is good.
3 calculus bovis factitius assays
Metho kahuangmin oral administration solution prescription (1) and the content of calculus bovis factitius in prescription (2) sample are measured, as a result seen Table 27.
27 metho kahuangmin oral solution assay result of table
Calculus bovis factitius content assaying method in 5 metho kahuangmin oral administration solutions
According to the above results, it is as follows to draft calculus bovis factitius content assaying method in metho kahuangmin oral administration solution:
The preparation of reference substance solution takes cholic acid reference substance 12.5mg, accurately weighed, sets in 25ml measuring bottle, adds 60% glacial acetic acid Solution makes to dissolve, and is diluted to scale, shakes up to get (containing cholic acid 0.5mg) in every 1ml.
The preparation precision of standard curve measures reference substance solution 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1ml, sets tool respectively It fills in test tube, each pipe is added 60% glacial acetic acid solution and is diluted to 1.0ml, then adds the furfuryl aldehyde solution (1 → 100) of brand-new respectively 1.0ml shakes up, and 5min is placed in ice bath, and sulfuric acid solution (sulfuric acid 50ml is taken to mix with water 65ml) 13ml is added in precision, mixes It is even, heat 10 minutes in 70 DEG C of water-baths, move in ice bath rapidly, place 2min, using corresponding reagent as blank, according to it is ultraviolet- Visible spectrophotometry (Chinese Pharmacopoeia version general rule 0401 in 2015) measures absorbance at the wavelength of 605nm, is with absorbance Ordinate, concentration are abscissa, draw standard curve.
Measuring method precision measures this product prescription 1. 100ml, prescription 2. 50ml, sets in separatory funnel, is saturated with water n-butanol It extracting 4 times, each 25ml, combined extract, water bath method, residue adds 60% glacial acetic acid to dissolve and is diluted in 25ml measuring bottle, It shakes up, filters, discard primary filtrate, precision measures each 1ml of subsequent filtrate, set in two tool plug test tubes of first, second respectively, in first Guan Zhongjia The furfuryl aldehyde solution 1ml of brand-new, second Guan Jiashui 1ml make blank, and the method under sighting target directrix curve preparation " is placed in ice bath certainly 5min " rise, measure absorbance in accordance with the law, from standard curve read test solution in the weight containing cholic acid, calculate to get.
Content limit: prescription 1.: every 1ml containing calculus bovis factitius with cholic acid (C24H40O5) meter, 55 μ g must not be less than；Prescription is 2.: Every 1ml is containing calculus bovis factitius with cholic acid (C24H40O5) meter, 110 μ g must not be less than.
The quality determining method of metho kahuangmin oral administration solution provided by the invention can simultaneously examine 15 kinds of compounds It surveys, control of the metho kahuangmin oral administration solution in relation to substance and calculus bovis factitius is effectively increased, so that metho kahuangmin oral administration solution Product Safety and validity have obtained better control；Simultaneously also overcome metho kahuangmin cannot be taken orally in existing method it is molten The problem of being detected in liquid in relation to substance and calculus bovis factitius content.
The foregoing is only a preferred embodiment of the present invention, but scope of protection of the present invention is not limited thereto, In the technical scope disclosed by the present invention, any changes or substitutions that can be easily thought of by anyone skilled in the art, It should be covered by the protection scope of the present invention.Therefore, protection scope of the present invention should be with scope of protection of the claims Subject to.

Claims (7)

1. a kind of quality determining method of metho kahuangmin oral administration solution, which is characterized in that the detection method includes: to amino Phenol, to chlorobenzene acetamide and in relation to the identification of substance, specific identification method is as follows:
1) preparation of test solution: taking this product prescription, 1. 2. appropriate, this product prescription is placed in measuring bottle, adds the first methanol aqueous solution It is diluted to scale, as test solution；
2) preparation of reference substance solution: taking p-aminophenol reference substance, appropriate to chlorobenzene acetamide reference substance respectively, accurately weighed, Add the second methanol aqueous solution to dissolve, is made respectively containing p-aminophenol, to the solution of chlorobenzene acetamide, as reference substance solution；
3) preparation of contrast solution: accurate measurement first reference substance solution and the test solution set same measuring bottle respectively In, it is diluted to scale with second methanol aqueous solution, is shaken up, as contrast solution；
4) high performance liquid chromatography Mass Spectrometer Method: being filler with octadecylsilane chemically bonded silica；It is stream with phosphate solution Dynamic phase A, using methanol as Mobile phase B, according to the form below carries out gradient elution；Detection wavelength is 200~250nm；Column temperature is 20~45 DEG C； Number of theoretical plate is calculated by paracetamol peak is not less than 2000, p-aminophenol, to chlorobenzene acetamide and paracetamol peak Separating degree should meet the requirements；Precision measures contrast solution and each 20 μ l of test solution, is injected separately into liquid chromatograph detection.
2. a kind of quality determining method of metho kahuangmin oral administration solution according to claim 1, which is characterized in that the step Rapid 1) specific step is as follows: taking that this product prescription is 1. appropriate, 2. 5ml is placed in 10ml measuring bottle to this product prescription, adds the body of methanol and water Product is than being (4~5): the methanol aqueous solution of (5~6) is diluted to scale, as test solution.
3. a kind of quality determining method of metho kahuangmin oral administration solution according to claim 2, which is characterized in that the step It is rapid that 2) specific step is as follows: p-aminophenol reference substance, appropriate to chlorobenzene acetamide reference substance is taken respectively, it is accurately weighed, and add institute The volume ratio for stating methanol and water is (4~5): the methanol aqueous solution of (5~6) dissolves, and is made in every lml respectively containing p-aminophenol 0.01 ~0.2mg~, to 0.01~0.2mg of chlorobenzene acetamide~solution, as reference substance solution.
4. a kind of quality determining method of metho kahuangmin oral administration solution according to claim 3, which is characterized in that the step Rapid 3) specific step is as follows: precision measures first reference substance solution and each 1ml of the test solution, sets same In 100ml measuring bottle, be (4~5) with the volume ratio of the methanol and water: the methanol aqueous solution of (5~6) is diluted to scale, shakes up, As contrast solution.
5. a kind of quality determining method of metho kahuangmin oral administration solution according to claim 4, which is characterized in that the step It is rapid 4) in, phosphate is made of or sodium dihydrogen phosphate and phosphoric acid potassium dihydrogen phosphate and dipotassium hydrogen phosphate in the phosphate solution Disodium hydrogen composition, and water is selected to prepare solution as solvent, the pH of the phosphate solution is 5.8~8.0.
6. a kind of quality determining method of metho kahuangmin oral administration solution according to claim 4, which is characterized in that the step It is rapid 4) in, Parameters of gradient elution are as follows:
7. a kind of quality determining method of metho kahuangmin oral administration solution, feature described in -6 any one according to claim 1 It is, the detection method further include: the identification to calculus bovis factitius, specific identification method are as follows:
1) preparation of cholic acid reference substance solution: taking cholic acid reference substance 12.5mg, accurately weighed, sets in 25ml measuring bottle, add 50~ 70% glacial acetic acid solution makes to dissolve, and is diluted to scale, shakes up, and cholic acid reference substance solution is made；
2) preparation of standard curve: precision measures cholic acid reference substance solution 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1ml, sets respectively In tool plug test tube, each pipe is added 50~70% glacial acetic acid solutions and is diluted to 1.0ml, then respectively plus the furfuryl aldehyde solution of brand-new (1 → 100) 1.0ml shakes up, and 4~6min is placed in ice bath, and sulfuric acid solution (sulfuric acid 50ml is taken to mix with water 65ml) is added in precision 13ml is mixed, is heated 10min in 70 DEG C of water-baths, move in ice bath, is placed 2 minutes, using corresponding reagent as blank；
3) UV-VIS spectrophotometry detects: measuring absorbance at the wavelength of 600~610nm, is vertical sit with absorbance Mark, concentration is abscissa, is detected；
4) accurate to measure this product prescription 1. 100ml, prescription 2. 50ml, it sets in separatory funnel, is saturated with water n-butanol and extracts 4 times, Each 25ml, combined extract, water bath method, residue add 60% glacial acetic acid to dissolve and are diluted in 25ml measuring bottle, shake up, filter It crosses, discards primary filtrate, precision measures each 1ml of subsequent filtrate, set in two tool plug test tubes of first, second respectively, in first Guan Zhongjia brand-new Furfuryl aldehyde solution 1ml, second Guan Jiashui 1ml make blank, the method under sighting target directrix curve preparation, from " placing 5min in ice bath " Rise, measure absorbance in accordance with the law, from standard curve read test solution in the weight containing cholic acid, calculate to get.
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CN115097049A (en) * 2022-07-25 2022-09-23 广西壮族自治区食品药品检验所 Method for determining related substances in pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate granules

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Application publication date: 20190716