CN104316482A - A quality control method for ambroxol hydrochloride particles - Google Patents
A quality control method for ambroxol hydrochloride particles Download PDFInfo
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Abstract
The invention belongs to the field of medicine analysis, and particularly relates to a quality control method for ambroxol hydrochloride particles. A quality control measure is developed for the ambroxol hydrochloride particles. The method is characterized in that: the dissolution rate and related compounds are controlled, and the method is accurate, stable and good in durability and can control product quality well.
Description
Technical field
The present invention relates to a kind of method of quality control of Ambroxol Hydrochloride Granules preparation, belong to Pharmaceutical Analysis field.
Background technology
Ambroxol Hydrochloride Granules Main Ingredients and Appearance is ambroxol hydrochloride, its chemical name: trans-4-[(amino-3, the 5-dibromo-benzyls of 2-) are amino] cyclohexanol hydrochloridumi.Be applicable to secrete abnormal and expectoration dysfunction acute, chronic respiratory disease, the treatment of eliminating the phlegm of such as chronic bronchitis acute exacerbation, asthma type brochitis, bronchiectasis and bronchial astehma with phlegm midnight.Preparation at present about ambroxol hydrochloride mainly contains injection, syrup, tablet, granule, capsule, effervescent tablet, oral disnitegration tablet, oral liquid, chewable tablets, sustained release preparation and dispersing tablet etc.Due to prescription and preparation technology's difference, detection method for these preparations is also different, does not also have the quality standard of ambroxol hydrochloride granula at present, therefore, we are according to the feature of ambroxol hydrochloride granula, grope through research the method for quality control obtaining Ambroxol Hydrochloride Granules.
Summary of the invention
Have no the relevant report of the method for quality control about ambroxol hydrochloride granula at present, the detection method of other formulation existing also may not be applicable to ambroxol hydrochloride granula.The present invention is directed to Ambroxol Hydrochloride Granules and establish quality control method, focus on controlling its dissolution rate and related substance, and method is accurate, stable, durability is good, can be good at controlling product quality.
Ambroxol Hydrochloride Granules of the present invention is prepared from by ambroxol hydrochloride and relevant auxiliary materials, and its preparation method is ambroxol hydrochloride, sucrose, sweet mellow wine mix after 80 mesh sieves, adds appropriate bonding agent (10% PVP K
3070% ethanolic solution) granulate, dry, add recipe quantity sweet orange powdered flavor and mix, to obtain final product.
Method of quality control of the present invention is mainly the control method of dissolution rate and related substance.
Described dissolution detection method is as follows: with the hydrochloric acid solution 900ml of 0.1mol/L for solvent, rotating speed is 50 turns per minute, through 30min, get solution to filter in right amount, precision measures subsequent filtrate 5ml in 10ml measuring bottle, the hydrochloric acid solution adding 0.1mol/L is diluted to scale, according to UV-VIS spectrophotometry, measures absorbance log at the wavelength place of 244nm; Separately get the ambroxol hydrochloride reference substance 30mg of 105 DEG C of dry constant weights, accurately weighed, put in 100ml measuring bottle, be diluted to scale, shake up, precision measures in right amount, the solution containing 15 μ g in every 1ml is diluted to the hydrochloric acid solution of 0.1mol/L, be measured in the same method absorbance log, calculate the stripping quantity of every bag, be not less than 80% of labelled amount.
The detection method of described related substance is as follows:
Chromatographic condition: octadecylsilane chemically bonded silica is filling agent; With 0.01mol/L ammonium dibasic phosphate solution (by phosphoric acid adjust ph to 7.0)-acetonitrile (50:50) for mobile phase; Determined wavelength is 248nm;
System suitability solution: get ambroxol hydrochloride reference substance 5mg, adds methyl alcohol 0.2ml and dissolves, then adds formalin 40 μ l, shakes up, and put 60 DEG C of heating 5 minutes, nitrogen dries up.Residue use water 5ml dissolves, then adds mobile phase and be diluted to 20ml.The degree of separation of ambroxol hydrochloride and impurity B (relative retention time is about 0.8) should be greater than 4.0;
Impurity B: take ambroxol hydrochloride impurity B reference substance appropriate, be configured to the impurity B reference substance solution of 2 μ g/ml with mobile phase;
Impurity B chemical name: trans-4-[the bromo-Isosorbide-5-Nitrae-dihydroquinazoline-3 (H) of 6,8-bis-] cyclohexanol, molecular formula is C
14h
18br
2n
2o,
Chemical formula is:
Impurity E: take ambroxol hydrochloride impurity B reference substance appropriate, be configured to the impurity E reference substance solution of 2 μ g/ml with mobile phase;
Amino-3, the 5-dibromo benzaldehydes of impurity E title: 2-, molecular formula is C
7h
5br
2nO,
Chemical formula is:
Need testing solution: Ambroxol Hydrochloride Granules is appropriate, and porphyrize, takes fine powder and dissolve with mobile phase in right amount and the solution being diluted to 1mg/ml, as need testing solution;
Own control solution: measure need testing solution 1ml mobile phase and be diluted to 100ml, obtain self contrast solution;
Measure need testing solution, impurity reference substance solution and each 20 μ l of own control solution, injection liquid chromatography, record chromatogram is to 3 times of major component peak retention time, if any impurity B and impurity E in the chromatogram of need testing solution, the content of its impurity must not be greater than 0.2% of major component, and other unknown single impurity peak area must not be greater than 0.2 times (0.2%) of the main peak area of contrast solution, each impurity peak area and 0.6 times (0.6%) of main peak area that must not be greater than contrast solution.
Reliable and stable in order to ensure method of quality control of the present invention, applicant has carried out methodological study to the dissolution rate in the method and related substance method, and specific experiment data is as follows:
(1) dissolution rate:
Stripping comparative study has been carried out with former triturate (Ambroxol Hydrochloride Tablets, Mucosolvin, Shanghai Boehringer Ingelheim pharmaceutcal corporation, Ltd), in four kinds of dissolution mediums, consistent with former triturate dissolved corrosion.Result is as follows:
1) pH 1.0 hydrochloric acid medium:
With the hydrochloric acid of 900ml pH 1.0 for medium (9ml hydrochloric acid is dissolved in 1000ml water), rotating speed is 50 revs/min, in the 5th, 10,15,30,45min sampling, filter, precision measures subsequent filtrate 5ml in 10ml measuring bottle, the hydrochloric acid solution adding 0.1mol/L is diluted to scale, according to UV-VIS spectrophotometry, measures absorbance log at the wavelength place of 244nm; Separately get the ambroxol hydrochloride reference substance 30mg of 105 DEG C of dry constant weights, accurately weighed, put in 100ml measuring bottle, add the dissolve with hydrochloric acid solution of 0.1mol/l and be diluted to scale, shake up, precision measures in right amount, is diluted to the solution containing 15 μ g in every 1ml with the hydrochloric acid solution of 0.1mol/l, be measured in the same method absorbance log, calculate the stripping quantity of every bag/sheet.See the following form:
Stripping curve in table 1 pH 1.0 hydrochloric acid medium
2) pH 4.5 acetate salt buffer liquid medium:
With 900ml pH 4.5 acetate buffer for medium (takes 2.99g sodium acetate, add 2mol/l acetum 14ml, be diluted with water to 1000ml), rotating speed is 50 revs/min, in the 5th, 10,15,30,45min sampling, filter, precision measures subsequent filtrate 5ml in 10ml measuring bottle, add pH 4.5 acetate buffer medium to scale, according to UV-VIS spectrophotometry, measure absorbance log at the wavelength place of 244nm; Separately get the ambroxol hydrochloride reference substance 30mg of 105 DEG C of dry constant weights, accurately weighed, put in 100ml measuring bottle, be diluted to scale by pH 4.5 acetate buffer medium dissolves, shake up, precision measures in right amount, becomes the solution containing 15 μ g in every 1ml by pH 4.5 acetate buffer medium, be measured in the same method absorbance log, calculate the stripping quantity of every bag/sheet.See the following form:
Stripping curve in table 2 pH 4.5 acetate salt buffer liquid medium
3) pH 6.8 phosphate-buffered liquid medium:
With 900ml pH 6.8 phosphate buffer for medium (is got after 250ml 0.2mol/L potassium dihydrogen phosphate mixes with the 0.2mol/L sodium hydroxide solution of 112ml, be diluted with water to 1000ml again), rotating speed is 50 revs/min, in the 5th, 10,15,30,45min sampling, filter, precision measures subsequent filtrate 5ml in 10ml measuring bottle, adds pH 6.8 phosphate buffer medium to scale, according to UV-VIS spectrophotometry, measure absorbance log at the wavelength place of 244nm; Separately get the ambroxol hydrochloride reference substance 30mg of 105 DEG C of dry constant weights, accurately weighed, put in 100ml measuring bottle, be diluted to scale by pH 6.8 phosphate buffer medium dissolves, shake up, precision measures in right amount, becomes the solution containing 15 μ g in every 1ml by pH 6.8 phosphate buffer medium, be measured in the same method absorbance log, calculate the stripping quantity of every bag/sheet.See the following form:
Stripping curve in table 3 pH 6.8 phosphate-buffered liquid medium
4) aqueous medium:
With 900ml water for medium, rotating speed is 50 revs/min, in the 5th, 10,15,30,45min sampling, filter, precision measures subsequent filtrate 5ml in 10ml measuring bottle, is diluted with water to scale, according to UV-VIS spectrophotometry, measures absorbance log at the wavelength place of 244nm; Separately get the ambroxol hydrochloride reference substance 30mg of 105 DEG C of dry constant weights, accurately weighed, put in 100ml measuring bottle, be diluted to scale by water-soluble solution, shake up, precision measures in right amount, be diluted with water to the solution containing 15 μ g in every 1ml, be measured in the same method absorbance log, calculate the stripping quantity of every bag/sheet.See the following form:
Stripping curve in table 4 water
(2) related substance:
Discovery is compared with ambroxol hydrochloride injection related substance detection method (see " import drugs meets standard JX19980021 ") in prior art, in this standard, in ambroxol hydrochloride injection related substance detection method, with phosphate buffer, (getting diammonium hydrogen phosphate 2g is dissolved in 800ml water, with phosphoric acid regulating ph value to 4.0, thin up becomes 1000ml again)-methyl alcohol (48:52) is mobile phase, after mobile phase configuration sample, in sample, impurity B is unstable, in rising tendency gradually, therefore, method in employing standard measures the detection of Ambroxol Hydrochloride Granules to impurity B and there is error, and with the inventive method mobile phase configuration sample solution good stability, measurement result is accurate.Comparative result is as follows:
Table 5 distinct methods sample solution stability compares
By illustrating the checking of the inventive method, this method is used for the detection of Ambroxol Hydrochloride Granules, and acquired results is accurate, and easy and simple to handle, concrete outcome is as follows:
1) specificity
Under strong acid, highly basic, Strong oxdiative, high temperature and illumination condition, strong degradation experiment is carried out to Ambroxol Hydrochloride Granules, investigate the degradation pathway of impurity and the separation degree with main peak.Blank auxiliary investigates auxiliary material to the impact of defects inspecting.Experimental result shows that the degree of separation of impurity and main peak is all greater than 2.0, blank auxiliary and the detection of blank solvent to impurity noiseless.See the following form:
The strong degradation experiment result of table 6
2) linear
Configure the ambroxol hydrochloride of variable concentrations, impurity B and impurity E solution respectively, measure its peak area, the calculated response factor, with concentration be horizontal ordinate (x), peak area is that ordinate (y) carries out linear regression analysis, and result is as follows:
Table 7 ambroxol hydrochloride Linear Experiment result
Table 8 ambroxol hydrochloride impurity B linear determination result
Table 9 ambroxol hydrochloride impurity E linear determination result
3) repeatability
Parallel preparation 6 parts of need testing solutions, the content of impurity in difference working sample, result shows that the related substance of the method mensuration Ambroxol Hydrochloride Granules is reproducible.See the following form:
The repeated measurement result of table 10
4) Intermediate precision
By different personnel, at different time parallel preparation 6 parts of need testing solutions respectively, the content of impurity in difference working sample, experimental result shows that the relative standard deviation of impurity content in 12 parts of need testing solutions is all not more than 20%, and the method precision is good.See the following form:
Table 11 Intermediate precision measurement result
5) detectability
By the need testing solution of concentration known and impurity reference substance solution stepwise dilution to low concentration, when the signal intensity recorded and the ratio of noise are about 3, corresponding sample size is detectability.Experimental result shows, the method is highly sensitive, can meet the inspection of sample related substance.See the following form:
Table 12 detectability experimental result
6) quantitative limit
By the need testing solution of concentration known and impurity reference substance solution stepwise dilution to low concentration, when the signal intensity recorded and the ratio of noise are about 10, corresponding sample size is quantitative limit;
Prepare 6 parts of quantitative limit strength solution, measure respectively, record retention time and peak area, result shows that the retention time relative standard deviation of 6 parts of solution is all less than 2.0%, and the relative standard deviation of peak area is all less than 5.0%, and method is accurate.See the following form:
Table 13 quantitative limit experimental result
7) durability
By changing ratio, the pH value of mobile phase, the lot number of note temperature, determined wavelength, flow velocity and chromatographic column of mobile phase, investigate chromatographic condition subtle change to the impact of dirt content test.Experimental result shows, the small variations of experiment condition can not affect the detection of impurity content, and the method durability is good.See the following form:
Table 14 durability experimental result
8) system suitability
The impurity reference substance solution of compounding system applicability solution and 6 parts of same concentrations is analyzed, and the degree of separation of impurity B and major component is greater than 4.0; The relative standard deviation of impurity peaks peak area is less than 2.0%; The relative standard deviation of retention time is less than 1.0%; The tailing factor of impurity peaks is all less than 2.0, and the method system suitability is good.See the following form:
Table 15 system suitability experimental result
Note: " N/A " is inapplicable
9) stability of solution
Preparation need testing solution, own control solution and impurity reference substance solution, and under above-mentioned need testing solution and own control solution are put room temperature, check respectively in 0h, 4h, 8h, 12h and 24h, calculate impurity content.Experimental result shows, the method is solution-stabilized within 24h.See the following form:
The solution-stabilized experimental result of table 16
10) the impurity recovery
The method that the recovery of known impurities adopts mark-on to reclaim measures, and adds the impurity contrast of 0.1%, 0.2%, 0.3% respectively in the sample to which, measures, compared by measured value with theoretical value, calculate the recovery.Experimental result shows that the recovery of impurity under each concentration is all at 80%-120%; Relative standard deviation is all less than 10%.See the following form:
Table 17 impurity recovery experimental result
11) contrast with former triturate
Carried out determination of related substances to Ambroxol Hydrochloride Granules and former triturate (Mucosolvin) respectively, result shows that the Ambroxol Hydrochloride Granules oneself prepared and former triturate are without significant difference;
Ambroxol Hydrochloride Granules preparation method: get sweet mellow wine, sucrose and pulverize respectively and cross 80 mesh sieves, get ambroxol hydrochloride raw material and cross 80 mesh sieves, take ambroxol hydrochloride 30g respectively, sweet mellow wine 370g, sucrose 800g mixes, and adds the PVP K of 10%
30ethanolic solution (70%) prepares softwood, and is granulated by 16 mesh sieves, and dry at putting 60 DEG C, in the whole grain of 10-40 mesh sieve, gained sample is Ambroxol Hydrochloride Granules.Prepare three batch samples (sample 1, sample 2, sample 3) by the method and detect related substance.See the following form:
Table 18 and former triturate related substance testing result
Accompanying drawing explanation
Fig. 1 is stripping curve figure in pH 1.0 hydrochloric acid medium
Fig. 2 is stripping curve figure in pH 4.5 acetate salt buffer liquid medium
Fig. 3 is stripping curve figure in pH 6.8 phosphate buffer
Fig. 4 is stripping curve figure in aqueous medium
Fig. 5 is ambroxol hydrochloride linear graph
Fig. 6 is impurity B linear graph
Fig. 7 is impurity E linear graph
Specific embodiment
Embodiment 1
Ambroxol Hydrochloride Granules sample determination:
Dissolution rate:
Measure 54ml concentrated hydrochloric acid and be diluted with water to 6000ml, obtain pH 1.0 hydrochloric acid medium, measure 6 parts of 900ml pH 1.0 hydrochloric acid mediums and be placed in 6 stripping rotors respectively, rotating speed is 50 revs/min, dissolution medium temperature is 37 DEG C, get and often criticize Ambroxol Hydrochloride Granules (sample 1, sample 2, sample 3) each 6 bags be placed in 6 stripping rotors respectively, in 30min sampling, filter, precision measures subsequent filtrate 5ml in 10ml measuring bottle, the hydrochloric acid solution adding 0.1mol/L is diluted to scale, according to UV-VIS spectrophotometry, measures absorbance log at the wavelength place of 244nm; Separately get the ambroxol hydrochloride reference substance 29.78mg of 105 DEG C of dry constant weights, accurately weighed, put in 100ml measuring bottle, be diluted to scale, shake up, precision measures 2.5ml, be diluted to 50ml with the hydrochloric acid solution of 0.1mol/L, be measured in the same method absorbance log, calculate the stripping quantity of every bag;
Related substance:
Mobile phase configures: take diammonium hydrogen phosphate 1.3205g and be dissolved in 1000ml water, regulate pH=7.0, mix with acetonitrile according to 50:50 with phosphoric acid, filters;
Chromatographic condition: chromatographic column take octadecylsilane chemically bonded silica as filling agent, flow velocity 1.0ml/min, and determined wavelength is 248nm;
System suitability solution allocation: get ambroxol hydrochloride reference substance 5.3mg, adds methyl alcohol 0.2ml and dissolves, then adds formalin 40 μ l, shakes up, and put 60 DEG C of heating 5 minutes, nitrogen dries up.Residue use water 5ml dissolves, then adds mobile phase and be diluted to 20ml.The degree of separation of ambroxol hydrochloride and impurity B (relative retention time is about 0.8) should be greater than 4.0;
Impurity B: take ambroxol hydrochloride impurity B reference substance 11.36mg and put in 100ml measuring bottle, adds mobile phase and dissolves and dilute and put scale, measures 1ml mobile phase and is diluted to 50ml and obtains impurity B reference substance solution;
Impurity E: take ambroxol hydrochloride impurity E reference substance 10.95mg and put in 100ml measuring bottle, adds mobile phase and dissolves and dilute and put scale, measures 1ml mobile phase and is diluted to 50ml and obtains impurity E reference substance solution;
Need testing solution: get three batches of (sample 1, sample 2, sample 3) Ambroxol Hydrochloride Granules appropriate, porphyrize respectively, taking fine powder 1.00761g, 1.00571g, 1.00293g puts in 25ml two bottles respectively, dissolve with mobile phase and be diluted to scale, as need testing solution 1, need testing solution 2, need testing solution 3;
Own control solution: measure need testing solution 1, need testing solution 2, each 1ml mobile phase of need testing solution 3 be diluted to 100ml, obtain self contrast solution 1, own control solution 2, own control solution 3;
Get each 20 μ l of above-mentioned each solution to detect according to described chromatographic condition, and calculate impurity B, impurity E, maximum unknown single assorted and content of always mixing.
Embodiment 2.
Mucosolvin sample determination:
Dissolution rate:
Measure 54ml concentrated hydrochloric acid and be diluted with water to 6000ml, obtain pH 1.0 hydrochloric acid medium, measure 6 parts of 900ml pH 1.0 hydrochloric acid mediums and be placed in 6 stripping rotors respectively, rotating speed is 50 revs/min, dissolution medium temperature is 37 DEG C, get 6 Mucosolvins and be placed in 6 stripping rotors respectively, in 30min sampling, filter, precision measures subsequent filtrate 5ml in 10ml measuring bottle, the hydrochloric acid solution adding 0.1mol/L is diluted to scale, according to UV-VIS spectrophotometry, measures absorbance log at the wavelength place of 244nm; Separately get the ambroxol hydrochloride reference substance 31.70mg of 105 DEG C of dry constant weights, accurately weighed, put in 100ml measuring bottle, be diluted to scale, shake up, precision measures 2.5ml, be diluted to 50ml with the hydrochloric acid solution of 0.1mol/L, be measured in the same method absorbance log, calculate the stripping quantity of every bag;
Related substance:
Mobile phase configures: take diammonium hydrogen phosphate 1.3198g and be dissolved in 1000ml water, regulate pH=7.0, mix with acetonitrile according to 50:50 with phosphoric acid, filters;
Chromatographic condition: chromatographic column take octadecylsilane chemically bonded silica as filling agent, flow velocity 1.0ml/min, and determined wavelength is 248nm;
System suitability solution allocation: get ambroxol hydrochloride reference substance 5.6mg, adds methyl alcohol 0.2ml and dissolves, then adds formalin 40 μ l, shakes up, and put 60 DEG C of heating 5 minutes, nitrogen dries up.Residue use water 5ml dissolves, then adds mobile phase and be diluted to 20ml.The degree of separation of ambroxol hydrochloride and impurity B (relative retention time is about 0.8) should be greater than 4.0;
Impurity B: take ambroxol hydrochloride impurity B reference substance 11.36mg and put in 100ml measuring bottle, adds mobile phase and dissolves and dilute and put scale, measures 1ml mobile phase and is diluted to 50ml and obtains impurity B reference substance solution;
Impurity E: take ambroxol hydrochloride impurity E reference substance 10.95mg and put in 100ml measuring bottle, adds mobile phase and dissolves and dilute and put scale, measures 1ml mobile phase and is diluted to 50ml and obtains impurity E reference substance solution;
Need testing solution: Mucosolvin 5 porphyrizes, takes fine powder 0.2002g and puts in 25ml two bottles, dissolve and be diluted to scale, as need testing solution with mobile phase;
Own control solution: measure need testing solution 1ml mobile phase and be diluted to 100ml, obtain self contrast solution;
Get each 20 μ l of above-mentioned each solution to detect according to described chromatographic condition, and calculate impurity B, impurity E, maximum unknown single assorted and content of always mixing.
Claims (8)
1. a method of quality control for Ambroxol Hydrochloride Granules, is characterized in that controlling its dissolution rate and related substance.
2. method of quality control as claimed in claim 1, the control method of the dissolution rate described in it is: with 0.1mol/l hydrochloric acid for dissolution medium, through sampling in 30 minutes, with ultraviolet-visible spectrophotometry for detection method, require that the stripping quantity of every bag must not lower than 80% of labelled amount.
3. method of quality control as claimed in claim 2, described in it, the control method of dissolution rate is as follows:
With 0.1mol/l hydrochloric acid solution 900ml for dissolution medium, rotating speed is 50 turns per minute, through sampling in 30 minutes, according to ultraviolet-visible spectrophotometry, by external standard method, measures absorbance log, require that the stripping quantity of every bag must not lower than 80% of labelled amount at 244nm wavelength place.
4. method of quality control as claimed in claim 3, described in it, the control method of dissolution rate is specially:
With the hydrochloric acid solution 900ml of 0.1mol/L for medium, rotating speed is 50 turns per minute, through 30 minutes, get solution to filter in right amount, precision measures subsequent filtrate 5ml in 10ml measuring bottle, the hydrochloric acid solution adding 0.1mol/L is diluted to scale, according to UV-VIS spectrophotometry, measures absorbance log at the wavelength place of 244nm; Separately get the ambroxol hydrochloride reference substance 30mg of 105 DEG C of dry constant weights, accurately weighed, put in 100ml measuring bottle, be diluted to scale, shake up, precision measures in right amount, the solution containing 15 μ g in every 1ml is diluted to the hydrochloric acid solution of 0.1mol/L, be measured in the same method absorbance log, calculate the stripping quantity of every bag, be not less than 80% of labelled amount.
5. method of quality control as claimed in claim 1, the control method of related substance described in it is:
According to high performance liquid chromatography, with ammonium dibasic phosphate solution-acetonitrile for mobile phase, determined wavelength is 248nm, requires that known impurities must not exceed 0.2% of major component, maximum unknown single mix must not exceed 0.2% of major component, total must not mix exceed 0.6% of major component.
6. method of quality control as claimed in claim 5, the control method of related substance described in it is:
According to high performance liquid chromatography, chromatographic column take octadecylsilane chemically bonded silica as filling agent; With 0.01mol/l ammonium dibasic phosphate solution-acetonitrile for mobile phase, determined wavelength is 248nm, and known impurities is B and E, requires that known impurities B and E all must not exceed 0.2% of major component, maximum unknown single mix must not exceed 0.2% of major component, total must not mix exceed 0.6% of major component;
Wherein, known impurities B is: trans-4-[the bromo-Isosorbide-5-Nitrae-dihydroquinazoline-3 (H) of 6,8-bis-] cyclohexanol, molecular formula is C
14h
18br
2n
2o;
Known impurities E is: amino-3, the 5-dibromo benzaldehydes of 2-, molecular formula is C
7h
5br
2nO.
7. method of quality control as claimed in claim 6, the control method of its related substance is:
According to high performance liquid chromatography, take octadecylsilane chemically bonded silica as filling agent; With 0.01mol/L ammonium dibasic phosphate solution-acetonitrile for mobile phase; Determined wavelength is 248nm;
Measure need testing solution, impurity reference substance solution and each 20 μ l of own control solution, injection liquid chromatography, record chromatogram is to 3 times of major component peak retention time, in measurement result, the content of impurity B and impurity E must not be greater than 0.2% of major component, other unknown single impurity peak area must not be greater than 0.2 times (0.2%) of the main peak area of contrast solution, each impurity peak area and 0.6 times (0.6%) of main peak area that must not be greater than contrast solution.
8. method of quality control as claimed in claim 7, the control method of related substance described in it is:
According to high performance liquid chromatography, take octadecylsilane chemically bonded silica as filling agent, mobile phase is 0.01mol/L ammonium dibasic phosphate solution: acetonitrile is 50:50, and 0.01mol/L ammonium dibasic phosphate solution phosphoric acid adjust ph to 7.0, determined wavelength is 248nm;
System suitability solution: get ambroxol hydrochloride reference substance 5mg, adds methyl alcohol 0.2ml and dissolves, then adds formalin 40 μ l, shakes up, and put 60 DEG C of heating 5 minutes, nitrogen dries up, and residue use water 5ml dissolves, then adds mobile phase and be diluted to 20ml; The relative retention time of ambroxol hydrochloride and impurity B is about 0.8, and degree of separation should be greater than 4.0;
Impurity B: take ambroxol hydrochloride impurity B reference substance appropriate, be configured to the impurity B reference substance solution of 2 μ g/ml with mobile phase;
Impurity E: take ambroxol hydrochloride impurity B reference substance appropriate, be configured to the impurity E reference substance solution of 2 μ g/ml with mobile phase;
Need testing solution: Ambroxol Hydrochloride Granules is appropriate, and porphyrize, takes fine powder and dissolve with mobile phase in right amount and the solution being diluted to 1mg/ml, as need testing solution;
Own control solution: measure need testing solution 1ml mobile phase and be diluted to 100ml, obtain self contrast solution.
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Cited By (2)
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| CN112540137A (en) * | 2020-12-08 | 2021-03-23 | 合肥远志医药科技开发有限公司 | Method for detecting organic impurities in ambroxol hydrochloride oral solution |
| CN113340833A (en) * | 2021-05-31 | 2021-09-03 | 珠海天凯生物科技有限公司 | Dissolution rate detection method of tannic acid particles |
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| CN113340833A (en) * | 2021-05-31 | 2021-09-03 | 珠海天凯生物科技有限公司 | Dissolution rate detection method of tannic acid particles |
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