CN102879517A - Quality testing method for compound paracetamol and amantadine hydrochloride granules - Google Patents
Quality testing method for compound paracetamol and amantadine hydrochloride granules Download PDFInfo
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- CN102879517A CN102879517A CN2012103768786A CN201210376878A CN102879517A CN 102879517 A CN102879517 A CN 102879517A CN 2012103768786 A CN2012103768786 A CN 2012103768786A CN 201210376878 A CN201210376878 A CN 201210376878A CN 102879517 A CN102879517 A CN 102879517A
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Abstract
The invention discloses a quality testing method for compound paracetamol and amantadine hydrochloride granules. The method mainly comprises the steps of appraising the quality of the compound paracetamol and amantadine hydrochloride granules by using a thin layer chromatography method, performing content uniformity measuring and content measuring for acetaminophen, amantadine hydrochloride, caffeine, chlorpheniramine maleate and artificial bezoar by using a liquid chromatography method, measuring the dissolution rate, and measuring the content of bilirubin to achieve the artificial bezoar content measuring. The quality testing method of micro samples of the compound paracetamol and amantadine hydrochloride granules is built, researches on appraisal, content measuring and content uniformity measuring of the compound paracetamol and amantadine hydrochloride granules are achieved, the accuracy is high, good in reproducibility, and the quality of the compound paracetamol and amantadine hydrochloride granules can be controlled comprehensively and effectively, so that clinical effects of the preparation are guaranteed.
Description
Technical field
The present invention relates to the quality determining method of medicine, relate in particular to a kind of quality determining method of Paracetamol and Amantadine Compound particle.
Background technology
Flu is by virus or bacterial disease, is a kind of self-healing property disease, is divided into generally common cold and influenza.Common cold, the traditional Chinese medical science claim " cold ", are a kind of respiratory tract common diseases that is caused by multiple virus, and wherein 30%-50% is that rhinovirus by certain serotype causes.Though common cold is mainly in early winter, in any season, as can occuring in spring, summer, the Causative virus of the flu of Various Seasonal is not just the same yet.Influenza is the Acute respiratory infectious disease that is caused by influenza virus.Virus is present in patient's the respiratory tract, in patient cough, give others through droplet infection when sneezing.
The cold drug that favored by the patient in the existing market; in the quality standard such as Paracetamol and Amantadine Compound sheet etc.; its quality determining method generally exists accuracy rate low; the problem that error is large; uniformity of dosage units such as caffeine detects; general method is to adopt titrimetry to detect; accuracy rate only has 80-90%; error is larger, in addition, and to the detection of calculus bovis factitius; general method is the content by determined by ultraviolet spectrophotometry cholerythrin or cholic acid; also there is the low problem of accuracy rate, and, during general application high performance liquid chromatography detection level; the detected sample consumption of required use is more; and can not accurately detect for the sample of trace, thereby provide a kind of accuracy rate height that has; favorable reproducibility, and can detect micro-example quality determining method have a very strong realistic meaning.
Summary of the invention
The quality determining method that the purpose of this invention is to provide a kind of Paracetamol and Amantadine Compound particle; wherein mainly comprise and utilize thin-layered chromatography to the Quality Identification of described Paracetamol and Amantadine Compound particle; utilize Determination of Content Uniformity and the assay of high performance liquid chromatography paracetamol, amantadine hydrochloride, caffeine, chlorphenamine maleate and calculus bovis factitius; and dissolution determination; the assay of wherein said calculus bovis factitius realizes that by Determination of Bilirubin Content By Highperformance Chrom Atogr accuracy rate is brought up to more than 99% at least.The present invention is by the preparation method's of mobile phase, test solution and the reference substance solution of high performance liquid chromatography improvement, and component concentration and uniformity of dosage units in can the Accurate Determining micro-example have the advantage of accuracy rate height, favorable reproducibility.
Technical scheme of the present invention is: a kind of quality determining method of Paracetamol and Amantadine Compound particle, wherein said Paracetamol and Amantadine Compound particle is by paracetamol 250g, amantadine hydrochloride 100g, caffeine 15g, chlorphenamine maleate 2g, calculus bovis factitius 10g, adds appropriate amount of auxiliary materials and makes 1000 bags; Wherein said quality determination mainly comprises and utilizes thin-layered chromatography to the Quality Identification of described Paracetamol and Amantadine Compound particle; utilize Determination of Content Uniformity and the assay of high performance liquid chromatography paracetamol, amantadine hydrochloride, caffeine, chlorphenamine maleate and calculus bovis factitius; and dissolution determination; the assay of wherein said calculus bovis factitius realizes that by Determination of Bilirubin Content By Highperformance Chrom Atogr described high performance liquid chromatography detects and is trace detection.
Preferably, in the quality determining method of described Paracetamol and Amantadine Compound particle, described bilirubinic content assaying method is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica, take methyl alcohol-methenyl choloride-0.1% phosphoric acid=88:6:6 as mobile phase, column temperature is 30 ℃; The detection wavelength is 449nm, and number of theoretical plate calculates by the cholerythrin peak and is not less than 1500;
The preparation of need testing solution: it is an amount of to get this product that is equivalent to approximately calculus bovis factitius 25mg, put in the 100ml conical flask, precision adds methenyl choloride-methanol-water-hydrochloric acid=90:10:0.3:0.03 mixed liquor 25ml, weighed weight, about 20 minutes of ultrasonic extraction, take out, be cooled to rapidly room temperature, weighed weight is again supplied with above-mentioned mixed liquor and to be subtracted weight loss, shake up, filter;
The preparation of reference substance solution: precision is measured cholerythrin reference substance 10mg, put in the brown measuring bottle of 100ml, it is an amount of to add methenyl choloride-methanol-water-hydrochloric acid=90:10:0.3:0.03 mixed liquor, about 20 minutes of ultrasonic dissolution, take out, be cooled to rapidly room temperature, add above-mentioned solvent dilution to scale, shake up, precision is measured 2ml, put in the brown measuring bottle of 25ml,, shake up to scale with above-mentioned solvent dilution;
Assay method: precision is measured need testing solution and each 10ul injection liquid chromatography of reference substance solution, measures, and get final product, the record chromatogram.
Preferably, in the quality determining method of described Paracetamol and Amantadine Compound particle, described paracetamol, content of caffeine assay method are as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Methanol-water=40:60 is mobile phase, detects wavelength 216nm, and number of theoretical plate calculates by the paracetamol peak should be not less than 1000, and the degree of separation at paracetamol peak and caffeine peak should meet the requirements;
The preparation of need testing solution: get the content under the content uniformity item, it is an amount of that porphyrize, precision take by weighing this product fine powder that is equivalent to approximately paracetamol 0.125g, puts in the tool plug triangular flask, the accurate ethanol 50ml that adds, jolting makes dissolving, filters, and precision is measured subsequent filtrate 10ml, put in the 50ml measuring bottle, thin up shakes up to scale, as need testing solution;
The preparation of reference substance solution: it is an amount of that precision takes by weighing 105 ℃ of paracetamol reference substance and caffeine reference substances that are dried to constant weight, add ethanol dissolving and water and quantitatively be diluted to the solution that contains approximately 0.5mg paracetamol and 0.03mg caffeine among every 1ml, in contrast product solution;
Assay method: precision is measured need testing solution and each 20 μ l of reference substance solution, difference injection liquid chromatography, the record chromatogram, by the amount of external standard method with calculated by peak area paracetamol and Caffeine Anhydrous, the amount of Caffeine Anhydrous multiply by 1.093, namely gets the content of C8H10N4O2H2O in the test sample.
Preferably, in the quality determining method of described Paracetamol and Amantadine Compound particle, described chlorphenamine maleate content assay method is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Acetonitrile-0.3% sodium dodecyl sulfate solution-phosphoric acid=60:40:0.02, triethylamine with adjusting pH value to 3.3 ± 0.1 is mobile phase, the detection wavelength is 210nm, and number of theoretical plate calculates by the chlorphenamine peak should be not less than 2000, and the degree of separation of chlorphenamine peak and adjacent peak should meet the requirements;
The preparation of need testing solution: get 1 bag of this product, porphyrize is put in the tool plug triangular flask, the accurate acetonitrile 25ml that adds, jolting makes dissolving, filters, and precision is measured subsequent filtrate 7.5ml and put in the 10ml measuring bottle, add 0.3% sodium dodecyl sulfate solution and be diluted to scale, shake up, as need testing solution;
The preparation of reference substance solution: it is an amount of that other precision takes by weighing 105 ℃ of chlorphenamine maleate reference substances that are dried to constant weight, adds the acetonitrile dissolving and quantitatively be diluted to the solution that every 1ml contains 0.06mg with 0.3% sodium dodecyl sulfate solution, in contrast product solution;
Assay method: precision is measured test liquid and each 20 μ l of reference substance solution, and the injection liquid chromatography records chromatogram respectively, by the amount of external standard method with the calculated by peak area chlorphenamine maleate.
Preferably, in the quality determining method of described Paracetamol and Amantadine Compound particle, the assay method of described amantadine hydrochloride content and uniformity of dosage units is as follows:
(1) content assaying method: get 20 bags of this product, accurately weighed, porphyrize, it is an amount of that precision takes by weighing this product that is equivalent to approximately amantadine hydrochloride 0.5g, put in the tool plug triangular flask, the accurate ethanol 200ml that adds, jolting makes dissolving, filters, precision is measured subsequent filtrate 100ml, put evaporate to dryness in the water-bath, residue adds water 20ml makes dissolving, adds 2 of bromophenol blue indicator solutions, dripping 36% acetum makes solution become yellow green by bluish violet, add 6 of bromophenol blue indicator solutions, fixed with 0.1mol/l silver nitrate titration drop, be gray purple to precipitating.Every 1ml0.1mol/l silver nitrate titration liquid is equivalent to the C10H17NHCl of 18.77mg;
(2) Determination of Content Uniformity method: get 1 bag of this product, porphyrize is put in the tool plug triangular flask, the accurate ethanol 200ml that adds, and jolting makes dissolving, filters, and precision is measured subsequent filtrate 100ml and is put evaporate to dryness in the water-bath; Residue adds water 20ml makes dissolving, adds 2 of bromophenol blue indicator solutions, drips 36% acetum and makes solution become yellow green by bluish violet; Add 6 of bromophenol blue indicator solutions, fixed with 0.1mol/L silver nitrate titration drop, be gray purple to precipitating; Every 1ml0.1mol/L silver nitrate titration liquid is equivalent to the C10H17NHCl of 18.77mg, should be up to specification.
Preferably, in the quality determining method of described Paracetamol and Amantadine Compound particle, the assay method of described dissolution rate is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Methanol-water=40:60 is mobile phase, detects wavelength 216nm, and number of theoretical plate calculates by the paracetamol peak should be not less than 1000, and the degree of separation at paracetamol peak and caffeine peak should meet the requirements;
The preparation of need testing solution: get 1 bag of this product, add watery hydrochloric acid 12ml, add water to 500ml, rotating speed is that per minute 50 turns, in accordance with the law operation, and in the time of 30 minutes, it is an amount of to get solution, filters, as need testing solution;
The preparation of reference substance solution: it is an amount of that other precision takes by weighing 105 ℃ of paracetamol reference substance and caffeine reference substances that are dried to constant weight, the solubilizer dissolving also quantitatively is diluted to the solution that contains approximately 0.5mg paracetamol and 0.03mg caffeine among every 1ml, in contrast product solution;
Assay method: measure according to method under the assay item, by the amount of external standard method with calculated by peak area paracetamol and Caffeine Anhydrous, the amount of Caffeine Anhydrous multiply by 1.093, namely gets the content of C8H10N4O2H2O in the test sample, limit should be 80% of labelled amount, should be up to specification.
Preferably, in the quality determining method of described Paracetamol and Amantadine Compound particle, the assay method of described Determination Paracetamol in Paracetamol uniformity coefficient is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Methyl alcohol-0.05mol/l ammonium acetate solution=15:85 is mobile phase, and the detection wavelength is 257nm, and number of theoretical plate calculates by the paracetamol peak should be not less than 5000;
The preparation of need testing solution: it is an amount of that precision takes by weighing this product fine powder that is equivalent to approximately paracetamol 100mg, puts in the 10ml measuring bottle, and it is an amount of to add mobile phase, jolting makes the paracetamol dissolving, adds mobile phase and is diluted to scale, shakes up, filter, get subsequent filtrate as need testing solution;
The preparation of reference substance solution: it is an amount of to get the p-aminophenol reference substance, accurately weighedly makes the solution that contains approximately 10 μ g among the 1ml, in contrast product solution with mobile phase dissolving and dilution;
Assay method: precision is measured above-mentioned two kinds of each 10 μ l of solution that face with new system, and the injection liquid chromatography records chromatogram respectively,, contains p-aminophenol and must not cross 0.1% of paracetamol labelled amount with calculated by peak area by external standard method.
The present invention has following beneficial effect: the quality determining method that a kind of Paracetamol and Amantadine Compound particle is provided; wherein mainly comprise and utilize thin-layered chromatography to the Quality Identification of described Paracetamol and Amantadine Compound particle; utilize Determination of Content Uniformity and the assay of liquid phase chromatography paracetamol, amantadine hydrochloride, caffeine, chlorphenamine maleate and calculus bovis factitius; and dissolution determination; the content of wherein said calculus bovis factitius realizes that by the bilirubinic content of high effective liquid chromatography for measuring accuracy rate is brought up to more than 99% at least.The present invention is by the preparation method's of mobile phase, test solution and the reference substance solution of high performance liquid chromatography improvement, and component concentration and uniformity of dosage units in can the Accurate Determining micro-example have the accuracy rate height, the advantage of favorable reproducibility.According to the quality determining method of Paracetamol and Amantadine Compound particle of the present invention, can control all-sidedly and accurately the quality of Paracetamol and Amantadine Compound particle, thereby guarantee the clinical efficacy of Paracetamol and Amantadine Compound particle.
Embodiment
The below elaborates to the present invention, can implement according to this after making those of ordinary skills consult this instructions.
A kind of quality determining method of Paracetamol and Amantadine Compound particle, wherein said Paracetamol and Amantadine Compound particle is by paracetamol 250g, amantadine hydrochloride 100g, caffeine 15g, chlorphenamine maleate 2g, calculus bovis factitius 10g, adds appropriate amount of auxiliary materials and makes 1000 bags; Wherein said quality determination mainly comprises and utilizes thin-layered chromatography to the Quality Identification of described Paracetamol and Amantadine Compound particle; utilize Determination of Content Uniformity and the assay of high performance liquid chromatography paracetamol, amantadine hydrochloride, caffeine, chlorphenamine maleate and calculus bovis factitius; and dissolution determination; the assay of wherein said calculus bovis factitius realizes that by Determination of Bilirubin Content By Highperformance Chrom Atogr described high performance liquid chromatography detects and is trace detection.
In the quality determining method of described Paracetamol and Amantadine Compound particle, described bilirubinic content assaying method is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica, take methyl alcohol-methenyl choloride-0.1% phosphoric acid=88:6:6 as mobile phase, column temperature is 30 ℃; The detection wavelength is 449nm, and number of theoretical plate calculates by the cholerythrin peak and is not less than 1500;
The preparation of need testing solution: it is an amount of to get this product that is equivalent to approximately calculus bovis factitius 25mg, put in the 100ml conical flask, precision adds methenyl choloride-methanol-water-hydrochloric acid=90:10:0.3:0.03 mixed liquor 25ml, weighed weight, about 20 minutes of ultrasonic extraction, take out, be cooled to rapidly room temperature, weighed weight is again supplied with above-mentioned mixed liquor and to be subtracted weight loss, shake up, filter;
The preparation of reference substance solution: precision is measured cholerythrin reference substance 10mg, put in the brown measuring bottle of 100ml, it is an amount of to add methenyl choloride-methanol-water-hydrochloric acid=90:10:0.3:0.03 mixed liquor, about 20 minutes of ultrasonic dissolution, take out, be cooled to rapidly room temperature, add above-mentioned solvent dilution to scale, shake up, precision is measured 2ml, put in the brown measuring bottle of 25ml,, shake up to scale with above-mentioned solvent dilution;
Assay method: precision is measured need testing solution and each 10ul injection liquid chromatography of reference substance solution, measures, and get final product, the record chromatogram.
In the quality determining method of described Paracetamol and Amantadine Compound particle, described paracetamol, content of caffeine assay method are as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Methanol-water=40:60 is mobile phase, detects wavelength 216nm, and number of theoretical plate calculates by the paracetamol peak should be not less than 1000, and the degree of separation at paracetamol peak and caffeine peak should meet the requirements;
The preparation of need testing solution: get the content under the content uniformity item, it is an amount of that porphyrize, precision take by weighing this product fine powder that is equivalent to approximately paracetamol 0.125g, puts in the tool plug triangular flask, the accurate ethanol 50ml that adds, jolting makes dissolving, filters, and precision is measured subsequent filtrate 10ml, put in the 50ml measuring bottle, thin up shakes up to scale, as need testing solution;
The preparation of reference substance solution: it is an amount of that precision takes by weighing 105 ℃ of paracetamol reference substance and caffeine reference substances that are dried to constant weight, add ethanol dissolving and water and quantitatively be diluted to the solution that contains approximately 0.5mg paracetamol and 0.03mg caffeine among every 1ml, in contrast product solution;
Assay method: precision is measured need testing solution and each 20 μ l of reference substance solution, difference injection liquid chromatography, the record chromatogram, by the amount of external standard method with calculated by peak area paracetamol and Caffeine Anhydrous, the amount of Caffeine Anhydrous multiply by 1.093, namely gets the content of C8H10N4O2H2O in the test sample.
In the quality determining method of described Paracetamol and Amantadine Compound particle, described chlorphenamine maleate content assay method is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Acetonitrile-0.3% sodium dodecyl sulfate solution-phosphoric acid=60:40:0.02, triethylamine with adjusting pH value to 3.3 ± 0.1 is mobile phase, the detection wavelength is 210nm, and number of theoretical plate calculates by the chlorphenamine peak should be not less than 2000, and the degree of separation of chlorphenamine peak and adjacent peak should meet the requirements;
The preparation of need testing solution: get 1 bag of this product, porphyrize is put in the tool plug triangular flask, the accurate acetonitrile 25ml that adds, jolting makes dissolving, filters, and precision is measured subsequent filtrate 7.5ml and put in the 10ml measuring bottle, add 0.3% sodium dodecyl sulfate solution and be diluted to scale, shake up, as need testing solution;
The preparation of reference substance solution: it is an amount of that other precision takes by weighing 105 ℃ of chlorphenamine maleate reference substances that are dried to constant weight, adds the acetonitrile dissolving and quantitatively be diluted to the solution that every 1ml contains 0.06mg with 0.3% sodium dodecyl sulfate solution, in contrast product solution;
Assay method: precision is measured test liquid and each 20 μ l of reference substance solution, and the injection liquid chromatography records chromatogram respectively, by the amount of external standard method with the calculated by peak area chlorphenamine maleate.
In the quality determining method of described Paracetamol and Amantadine Compound particle, the assay method of described amantadine hydrochloride content and uniformity of dosage units is as follows:
(1) content assaying method: get 20 bags of this product, accurately weighed, porphyrize, it is an amount of that precision takes by weighing this product that is equivalent to approximately amantadine hydrochloride 0.5g, put in the tool plug triangular flask, the accurate ethanol 200ml that adds, jolting makes dissolving, filters, precision is measured subsequent filtrate 100ml, put evaporate to dryness in the water-bath, residue adds water 20ml makes dissolving, adds 2 of bromophenol blue indicator solutions, dripping 36% acetum makes solution become yellow green by bluish violet, add 6 of bromophenol blue indicator solutions, fixed with 0.1mol/l silver nitrate titration drop, be gray purple to precipitating.Every 1ml0.1mol/l silver nitrate titration liquid is equivalent to the C10H17NHCl of 18.77mg;
(2) Determination of Content Uniformity method: get 1 bag of this product, porphyrize is put in the tool plug triangular flask, the accurate ethanol 200ml that adds, and jolting makes dissolving, filters, and precision is measured subsequent filtrate 100ml and is put evaporate to dryness in the water-bath; Residue adds water 20ml makes dissolving, adds 2 of bromophenol blue indicator solutions, drips 36% acetum and makes solution become yellow green by bluish violet; Add 6 of bromophenol blue indicator solutions, fixed with 0.1mol/L silver nitrate titration drop, be gray purple to precipitating; Every 1ml0.1mol/L silver nitrate titration liquid is equivalent to the C10H17NHCl of 18.77mg, should be up to specification.
In the quality determining method of described Paracetamol and Amantadine Compound particle, the assay method of described dissolution rate is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Methanol-water=40:60 is mobile phase, detects wavelength 216nm, and number of theoretical plate calculates by the paracetamol peak should be not less than 1000, and the degree of separation at paracetamol peak and caffeine peak should meet the requirements;
The preparation of need testing solution: get 1 bag of this product, add watery hydrochloric acid 12ml, add water to 500ml, rotating speed is that per minute 50 turns, in accordance with the law operation, and in the time of 30 minutes, it is an amount of to get solution, filters, as need testing solution;
The preparation of reference substance solution: it is an amount of that other precision takes by weighing 105 ℃ of paracetamol reference substance and caffeine reference substances that are dried to constant weight, the solubilizer dissolving also quantitatively is diluted to the solution that contains approximately 0.5mg paracetamol and 0.03mg caffeine among every 1ml, in contrast product solution;
Assay method: measure according to method under the assay item, by the amount of external standard method with calculated by peak area paracetamol and Caffeine Anhydrous, the amount of Caffeine Anhydrous multiply by 1.093, namely gets the content of C8H10N4O2H2O in the test sample, limit should be 80% of labelled amount, should be up to specification.
In the quality determining method of described Paracetamol and Amantadine Compound particle, the assay method of described Determination Paracetamol in Paracetamol uniformity coefficient is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Methyl alcohol-0.05mol/l ammonium acetate solution=15:85 is mobile phase, and the detection wavelength is 257nm, and number of theoretical plate calculates by the paracetamol peak should be not less than 5000;
The preparation of need testing solution: it is an amount of that precision takes by weighing this product fine powder that is equivalent to approximately paracetamol 100mg, puts in the 10ml measuring bottle, and it is an amount of to add mobile phase, jolting makes the paracetamol dissolving, adds mobile phase and is diluted to scale, shakes up, filter, get subsequent filtrate as need testing solution;
The preparation of reference substance solution: it is an amount of to get the p-aminophenol reference substance, accurately weighedly makes the solution that contains approximately 10 μ g among the 1ml, in contrast product solution with mobile phase dissolving and dilution;
Assay method: precision is measured above-mentioned two kinds of each 10 μ l of solution that face with new system, and the injection liquid chromatography records chromatogram respectively,, contains p-aminophenol and must not cross 0.1% of paracetamol labelled amount with calculated by peak area by external standard method.
In the quality determining method of described Paracetamol and Amantadine Compound particle, the method for described Quality Identification comprises:
(1) it is an amount of to get this product fine powder that is equivalent to approximately paracetamol 200mg, adds chloroform 30ml and makes dissolving, filters, and solution is put evaporate to dryness in the water-bath, and residue adds chloroform 3ml makes dissolving, filters, and washs residue with chloroform, reaches 5ml to filtrate, as need testing solution; Other gets paracetamol reference substance 100mg, chlorphenamine maleate reference substance 10mg, caffeine reference substance 10mg, amantadine hydrochloride reference substance 50mg, mixes, and adds chloroform 10ml and makes dissolving, filters, in contrast product solution; Test according to the thin-layered chromatography that second appendix V of Chinese Pharmacopoeia version in 2005 B includes, draw each 20 μ l of above-mentioned two kinds of solution, put respectively on same silica GF254 thin layer plate, take chloroform-methanol-acetone-liquor ammoniae fortis=9:1.5:1:0.012 as developping agent, after the expansion, take out, dry, put under the 254nm ultraviolet lamp and inspect; Show three fluorescence spots in the chromatogram of test solution, spray again with rare bismuth potassium iodide solution and make colour developing, should be two color dots, need testing solution the position of aobvious fluorescence spot and color dot should be identical with fluorescence spot and the color dot that corresponding reference substance solution is shown with color.
(2) it is an amount of to get this product fine powder that is equivalent to approximately calculus bovis factitius 20mg, adds chloroform 50ml, and ultrasonic processing 30 minutes filters, and filtrate is put evaporate to dryness in the water-bath, and residue adds methyl alcohol 1ml makes dissolving, as need testing solution; Other gets cholic acid, hyodesoxycholic acid reference substance, adds respectively methyl alcohol and makes the solution that contains 1mg among every 1ml, in contrast product solution.Test according to the thin-layered chromatography that second appendix V of Chinese Pharmacopoeia version in 2005 B includes, draw each 4 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, take isooctane-ethyl acetate-glacial acetic acid=15:7:5 as developping agent, after the expansion, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 105 ℃, puts under the 365nm ultraviolet lamp and inspects; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, the fluorescence spot of aobvious two same colors.
Although this practical working of an invention scheme is open as above, but it is not restricted to listed utilization in instructions and the embodiment, it can be applied to various suitable the field of the invention fully, for those skilled in the art, can easily realize other modification, therefore do not deviating under the universal that claim and equivalency range limit, the present invention is not limited to specific details.
Claims (7)
1. the quality determining method of a Paracetamol and Amantadine Compound particle, wherein said Paracetamol and Amantadine Compound particle is by paracetamol 250g, amantadine hydrochloride 100g, caffeine 15g, chlorphenamine maleate 2g, calculus bovis factitius 10g, adds appropriate amount of auxiliary materials and makes 1000 bags; Wherein said quality testing mainly comprises and utilizes thin-layered chromatography to the Quality Identification of described Paracetamol and Amantadine Compound particle; utilize Determination of Content Uniformity and the assay of high performance liquid chromatography paracetamol, amantadine hydrochloride, caffeine, chlorphenamine maleate and calculus bovis factitius; and dissolution determination; the assay of wherein said calculus bovis factitius realizes that by Determination of Bilirubin Content By Highperformance Chrom Atogr described high performance liquid chromatography detects and is trace detection.
2. the quality determining method of Paracetamol and Amantadine Compound particle as claimed in claim 1, wherein said bilirubinic content assaying method is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica, take methyl alcohol-methenyl choloride-0.1% phosphoric acid=88:6:6 as mobile phase, column temperature is 30 ℃; The detection wavelength is 449nm, and number of theoretical plate calculates by the cholerythrin peak and is not less than 1500;
The preparation of need testing solution: it is an amount of to get this product that is equivalent to approximately calculus bovis factitius 25mg, put in the 100ml conical flask, precision adds methenyl choloride-methanol-water-hydrochloric acid=90:10:0.3:0.03 mixed liquor 25ml, weighed weight, about 20 minutes of ultrasonic extraction, take out, be cooled to rapidly room temperature, weighed weight is again supplied with above-mentioned mixed liquor and to be subtracted weight loss, shake up, filter;
The preparation of reference substance solution: precision is measured cholerythrin reference substance 10mg, put in the brown measuring bottle of 100ml, it is an amount of to add methenyl choloride-methanol-water-hydrochloric acid=90:10:0.3:0.03 mixed liquor, about 20 minutes of ultrasonic dissolution, take out, be cooled to rapidly room temperature, add above-mentioned solvent dilution to scale, shake up, precision is measured 2ml, put in the brown measuring bottle of 25ml,, shake up to scale with above-mentioned solvent dilution;
Assay method: precision is measured need testing solution and each 10ul injection liquid chromatography of reference substance solution, measures, and get final product, the record chromatogram.
3. the quality determining method of Paracetamol and Amantadine Compound particle as claimed in claim 1 or 2, wherein said paracetamol, content of caffeine assay method are as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Methanol-water=40:60 is mobile phase, detects wavelength 216nm, and number of theoretical plate calculates by the paracetamol peak should be not less than 1000, and the degree of separation at paracetamol peak and caffeine peak should meet the requirements;
The preparation of need testing solution: get the content under the content uniformity item, it is an amount of that porphyrize, precision take by weighing this product fine powder that is equivalent to approximately paracetamol 0.125g, puts in the tool plug triangular flask, the accurate ethanol 50ml that adds, jolting makes dissolving, filters, and precision is measured subsequent filtrate 10ml, put in the 50ml measuring bottle, thin up shakes up to scale, as need testing solution;
The preparation of reference substance solution: it is an amount of that precision takes by weighing 105 ℃ of paracetamol reference substance and caffeine reference substances that are dried to constant weight, add ethanol dissolving and water and quantitatively be diluted to the solution that contains approximately 0.5mg paracetamol and 0.03mg caffeine among every 1ml, in contrast product solution;
Assay method: precision is measured need testing solution and each 20 μ l of reference substance solution, difference injection liquid chromatography, the record chromatogram, by the amount of external standard method with calculated by peak area paracetamol and Caffeine Anhydrous, the amount of Caffeine Anhydrous multiply by 1.093, namely gets the content of C8H10N4O2H2O in the test sample.
4. the quality determining method of Paracetamol and Amantadine Compound particle as claimed in claim 1 or 2, wherein said chlorphenamine maleate content assay method is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Acetonitrile-0.3% sodium dodecyl sulfate solution-phosphoric acid=60:40:0.02, triethylamine with adjusting pH value to 3.3 ± 0.1 is mobile phase, the detection wavelength is 210nm, and number of theoretical plate calculates by the chlorphenamine peak should be not less than 2000, and the degree of separation of chlorphenamine peak and adjacent peak should meet the requirements;
The preparation of need testing solution: get 1 bag of this product, porphyrize is put in the tool plug triangular flask, the accurate acetonitrile 25ml that adds, jolting makes dissolving, filters, and precision is measured subsequent filtrate 7.5ml and put in the 10ml measuring bottle, add 0.3% sodium dodecyl sulfate solution and be diluted to scale, shake up, as need testing solution;
The preparation of reference substance solution: it is an amount of that other precision takes by weighing 105 ℃ of chlorphenamine maleate reference substances that are dried to constant weight, adds the acetonitrile dissolving and quantitatively be diluted to the solution that every 1ml contains 0.06mg with 0.3% sodium dodecyl sulfate solution, in contrast product solution;
Assay method: precision is measured test liquid and each 20 μ l of reference substance solution, and the injection liquid chromatography records chromatogram respectively, by the amount of external standard method with the calculated by peak area chlorphenamine maleate.
5. the quality determining method of Paracetamol and Amantadine Compound particle as claimed in claim 1 or 2, the assay method of wherein said amantadine hydrochloride content and uniformity of dosage units is as follows:
(1) content assaying method: get 20 bags of this product, accurately weighed, porphyrize, it is an amount of that precision takes by weighing this product that is equivalent to approximately amantadine hydrochloride 0.5g, put in the tool plug triangular flask, the accurate ethanol 200ml that adds, jolting makes dissolving, filters, precision is measured subsequent filtrate 100ml, put evaporate to dryness in the water-bath, residue adds water 20ml makes dissolving, adds 2 of bromophenol blue indicator solutions, dripping 36% acetum makes solution become yellow green by bluish violet, add 6 of bromophenol blue indicator solutions, fixed with 0.1mol/l silver nitrate titration drop, be gray purple to precipitating.Every 1ml0.1mol/l silver nitrate titration liquid is equivalent to the C10H17NHCl of 18.77mg;
(2) Determination of Content Uniformity method: get 1 bag of this product, porphyrize is put in the tool plug triangular flask, the accurate ethanol 200ml that adds, and jolting makes dissolving, filters, and precision is measured subsequent filtrate 100ml and is put evaporate to dryness in the water-bath; Residue adds water 20ml makes dissolving, adds 2 of bromophenol blue indicator solutions, drips 36% acetum and makes solution become yellow green by bluish violet; Add 6 of bromophenol blue indicator solutions, fixed with 0.1mol/L silver nitrate titration drop, be gray purple to precipitating; Every 1ml0.1mol/L silver nitrate titration liquid is equivalent to the C10H17NHCl of 18.77mg, should be up to specification.
6. the quality determining method of Paracetamol and Amantadine Compound particle as claimed in claim 1 or 2, the assay method of wherein said dissolution rate is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Methanol-water=40:60 is mobile phase, detects wavelength 216nm, and number of theoretical plate calculates by the paracetamol peak should be not less than 1000, and the degree of separation at paracetamol peak and caffeine peak should meet the requirements;
The preparation of need testing solution: get 1 bag of this product, add watery hydrochloric acid 12ml, add water to 500ml, rotating speed is that per minute 50 turns, in accordance with the law operation, and in the time of 30 minutes, it is an amount of to get solution, filters, as need testing solution;
The preparation of reference substance solution: it is an amount of that other precision takes by weighing 105 ℃ of paracetamol reference substance and caffeine reference substances that are dried to constant weight, the solubilizer dissolving also quantitatively is diluted to the solution that contains approximately 0.5mg paracetamol and 0.03mg caffeine among every 1ml, in contrast product solution;
Assay method: measure according to method under the assay item, by the amount of external standard method with calculated by peak area paracetamol and Caffeine Anhydrous, the amount of Caffeine Anhydrous multiply by 1.093, namely gets the content of C8H10N4O2H2O in the test sample, limit should be 80% of labelled amount, should be up to specification.
7. the quality determining method of Paracetamol and Amantadine Compound particle as claimed in claim 1 or 2, the assay method of wherein said Determination Paracetamol in Paracetamol uniformity coefficient is as follows:
According to two appendix V of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: be filling agent with octadecylsilane chemically bonded silica; Methyl alcohol-0.05mol/l ammonium acetate solution=15:85 is mobile phase, and the detection wavelength is 257nm, and number of theoretical plate calculates by the paracetamol peak should be not less than 5000;
The preparation of need testing solution: it is an amount of that precision takes by weighing this product fine powder that is equivalent to approximately paracetamol 100mg, puts in the 10ml measuring bottle, and it is an amount of to add mobile phase, jolting makes the paracetamol dissolving, adds mobile phase and is diluted to scale, shakes up, filter, get subsequent filtrate as need testing solution;
The preparation of reference substance solution: it is an amount of to get the p-aminophenol reference substance, accurately weighedly makes the solution that contains approximately 10 μ g among the 1ml, in contrast product solution with mobile phase dissolving and dilution;
Assay method: precision is measured above-mentioned two kinds of each 10 μ l of solution that face with new system, and the injection liquid chromatography records chromatogram respectively,, contains p-aminophenol and must not cross 0.1% of paracetamol labelled amount with calculated by peak area by external standard method.
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| CN106525994A (en) * | 2016-09-19 | 2017-03-22 | 山西好医生药业有限公司 | Method for determination of related substances of paracetamol and tramadol hydrochloride capsules |
| CN107014911A (en) * | 2017-02-28 | 2017-08-04 | 吉林修正药业新药开发有限公司 | A kind of quality determining method for feeling capsule for curing |
| CN108254464A (en) * | 2018-01-16 | 2018-07-06 | 吉林修正药业新药开发有限公司 | The method of quality control of Fufang Anfenwanan capsules |
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