CN103837611A - Detection method of relevant substance of ambroxol hydrochloride injection - Google Patents
Detection method of relevant substance of ambroxol hydrochloride injection Download PDFInfo
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- CN103837611A CN103837611A CN201210486525.1A CN201210486525A CN103837611A CN 103837611 A CN103837611 A CN 103837611A CN 201210486525 A CN201210486525 A CN 201210486525A CN 103837611 A CN103837611 A CN 103837611A
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Abstract
The invention belongs to the field of pharmaceutical analysis, and more particularly relates to a detection method for determining a relavent substance of an ambroxol hydrochloride injection by adopting a high performance liquid chromatography. Compared with other methods, the method has the advantage that ambroxol hydrochloride and five known impurities can be effectively separated under the same liquid phase condition; meanwhile, the invention provides a novel detection method of an impurity B and an impurity D in the ambroxol hydrochloride injection, thereby determining the relevant substance in the ambroxol hydrochloride injection accurately and effectively, and achieving the purpose of accurately controlling the product quality.
Description
Technical field
The invention belongs to Pharmaceutical Analysis field, more particularly, is a kind of detection method that adopts ambroxol hydrochloride injection by HPLC related substance.
Background technology
Nomenclature of drug: ambroxol hydrochloride injection
English name: Ambroxol Hydrochloride Injection
Chemical name: the amino 3.5-dibromo-benzyl of trans-4-[(2-) amino] cyclohexanol hydrochloride
Structural formula:
Molecular formula: C
13h
18br
2n
2oHCl
Molecular weight: 414.6
Ambroxol hydrochloride is the metabolic product of bromhexine in human body, is that a kind of new glutinous phlegm dissolves medicine, is that current curative effect is affirmed, most widely used expelling phlegm drugs.The characteristic that this medical instrument has mucus to get rid of facilitation and dissolve secretion, it can promote the eliminating of thick secretions in respiratory tract and the delay of minimizing mucus, thereby significantly promotes expectoration, improves breath state.Application is when effect of ambroxol in treating, and the secretion of patient's mucus can return to normal condition, and cough and amount of expectoration significantly reduce conventionally, the surface reactive material of respiratory mucosa thereby can bring into play its normal defencive function.Ambroxol hydrochloride tolerance is good, can long-term taking.Mainly be applicable to acute, the chronic respiratory disease of and expectoration dysfunction undesired with sputum secretion, the therapy of eliminating the phlegm of for example chronic bronchitis acute exacerbation, asthma type brochitis and bronchial astehma; The prophylactic treatment of hand postoperative pulmonary complications; The treatment of premature and neonatal infant respiratory distress syndrome (IRDS).
The distribution of ambroxol hydrochloride from blood to tissue is fast and remarkable, is mainly distributed in lung, liver, kidney, is about 7 hours plasma half-life, without cumulative effect.Mainly, at liver metabolism, 90% is removed by kidney, and metabolic product is bromine ortho-aminobenzoic acid, and its biologically active is indefinite.
At present, in European Pharmacopoeia and British Pharmacopoeia, the known impurities of ambroxol hydrochloride has 5, is respectively: ambroxol hydrochloride impurity A, ambroxol hydrochloride impurity B, ambroxol hydrochloride impurity C, ambroxol hydrochloride impurity D and ambroxol hydrochloride impurity E.
Impurity A impurity B
Impurity C impurity D
Impurity E
In existing detection ambroxol hydrochloride injection, the correlation technique of related substance has:
1, " Chinese Pharmacopoeia " version in 2010 is not included the standard of ambroxol hydrochloride injection at present, has only included ambroxol hydrochloride raw material, solid pharmaceutical preparation and oral solution standard, and wherein the assay method of ambroxol hydrochloride raw material related substance is as follows:
Sample thief, dissolves and makes in every 1ml the solution containing 1mg with mobile phase, as need testing solution; Precision measures need testing solution 1ml, puts in 100ml measuring bottle, is diluted to scale with mobile phase, shakes up, in contrast solution.Get contrast solution 20 μ l injection liquid chromatographies, regulate detection sensitivity, make the peak height of major component chromatographic peak be about the 20%-25% of registering instrument full scale; Then precision measures need testing solution and the each 20 μ l injection liquid chromatographies of contrast solution respectively, records 2 times to major component peak retention time of chromatogram.In need testing solution if any impurity peaks, each impurity peak area and must not be greater than contrast solution main peak area, total impurities must not be greater than 1%.The chromatographic condition adopting is filling agent for adopting octadecylsilane chemically bonded silica; (regulate pH value to 7.0) ︰ acetonitrile=(50 ︰ 50) as mobile phase with phosphoric acid solution taking 0.01mol/L ammonium dibasic phosphate solution; Detect wavelength 248nm.
2, CN101865891A: a kind of detection method of ambroxol hydrochloride discloses impurity A (2-amino-3,5-dibromo benzaldehyde), be ambroxol hydrochloride known impurities E and impurity B (trans-4-[6,8-bis-bromo-1,4-dihydroquinazoline-3 (2H)] cyclohexanol) high efficiency liquid phase detection method, its chromatographic condition is: octadecylsilane chemically bonded silica is filling agent; Mobile phase is 0.01mol/L ammonium dibasic phosphate solution (with phosphorus acid for adjusting pH value to 7.0) ︰ acetonitrile=(50 ︰ 50); Detection wavelength is that the reference substance detection wavelength of impurity A and impurity B is 248nm, and it is 238nm that test sample detects wavelength.
3, CN102262135A: the detection method of ambroxol hydrochloride injection impurity and content assaying method disclose impurity B (trans-4-[6,8-bis-bromo-1,4-dihydroquinazoline-3 (2H)] cyclohexanol) and impurity E (2-amino-3,5-dibromo benzaldehyde) high efficiency liquid phase detection method, its chromatographic condition is: octadecylsilane chemically bonded silica is filling agent; Mobile phase is phosphate buffer-methyl alcohol volume ratio: 45-55 ︰ 55-45; Wherein, phosphate buffer is by diammonium hydrogen phosphate-phosphoric acid buffer to forming, and wherein the concentration of diammonium hydrogen phosphate is 0.002g/ml, pH of cushioning fluid is 4.0, and flow velocity is 1.0ml/min, and column temperature is 35 DEG C, the detection wavelength of impurity B is 250nm, and the detection wavelength of impurity E is 238nm.
Adopt above three kinds of related detection methods to carry out finding after liquid phase analysis to ambroxol hydrochloride injection and five kinds of known impurities: above three kinds of detection methods cannot effectively separate five kinds of known impurities of ambroxol hydrochloride under same liquid-phase condition, and by great many of experiments and exploration, in ambroxol hydrochloride injection of the present invention, related substance detection method can effectively separate ambroxol hydrochloride and five kinds of known impurities.
In ambroxol hydrochloride injection involved in the present invention, major impurity is impurity B and impurity D.Impurity B (trans-4-[6, bromo-Isosorbide-5-Nitrae-dihydroquinazoline-3 of 8-bis-(2H)] cyclohexanol, molecular formula is: C
14h
18br
2n
2and impurity D(cis-4-[(2-amino-3 O), 5-dibromobenzene methyl) amino] cyclohexanol, molecular formula is: C
13h
18br
2n
2o) be the catabolite of ambroxol hydrochloride.
At present, Chinese Pharmacopoeia in the condition determination of ambroxol hydrochloride related substance not the known impurities to ambroxol hydrochloride limit, quality standard set not high.In published patent, CN101865891A: a kind of detection method of ambroxol hydrochloride discloses self-defined impurity A (2-amino-3,5-dibromo benzaldehyde), be ambroxol hydrochloride known impurities E and impurity B (trans-4-[6,8-bis-bromo-1,4-dihydroquinazoline-3 (2H)] cyclohexanol) high efficiency liquid phase detection method, its chromatographic condition is: octadecylsilane chemically bonded silica is filling agent; Mobile phase is 0.01mol/L ammonium dibasic phosphate solution (with phosphorus acid for adjusting pH value to 7.0) ︰ acetonitrile=(50 ︰ 50); Detection wavelength is that the reference substance detection wavelength of impurity A and impurity B is 248nm, and it is 238nm that test sample detects wavelength.Another patent CN102262135A: the detection method of ambroxol hydrochloride injection impurity and content assaying method disclose impurity B (trans-4-[6,8-bis-bromo-1,4-dihydroquinazoline-3 (2H)] cyclohexanol) and impurity E (2-amino-3,5-dibromo benzaldehyde) high efficiency liquid phase detection method, its chromatographic condition is: octadecylsilane chemically bonded silica is filling agent; Mobile phase is phosphate buffer-methyl alcohol volume ratio: 45-55 ︰ 55-45; Wherein, phosphate buffer is by diammonium hydrogen phosphate-phosphoric acid buffer to forming, and wherein the concentration of diammonium hydrogen phosphate is 0.002g/ml, pH of cushioning fluid is 4.0, and flow velocity is 1.0ml/min, and column temperature is 35 DEG C, the detection wavelength of impurity B is 250nm, and the detection wavelength of impurity E is 238nm.From the impurity of concrete restriction, two patents are all restrictions that impurity B to ambroxol and impurity E carry out, the ambroxol hydrochloride raw material sources used due to each inventor are all not identical, in inventor's ambroxol raw material used and preparation, impurity E does not all detect, and impurity B and impurity D need to limit.
For this reason, the invention provides the detection method of impurity B and impurity D in a kind of new ambroxol hydrochloride injection, measure the related substance in ambroxol hydrochloride injection thereby realize accurate and effective, reach the object of precisely control product quality.
Summary of the invention
The invention provides a kind of accurate and effective and measure the method for the related substance in ambroxol hydrochloride injection, for detection of the impurity B in ambroxol hydrochloride injection and impurity D.
Impurity B of the present invention is trans-4-[6, bromo-Isosorbide-5-Nitrae-dihydroquinazoline-3 of 8-bis-(2H)] cyclohexanol, molecular formula is: C
14h
18br
2n
2o; Described impurity D is cis-4-[(2-amino-3,5-dibromobenzene methyl) amino] cyclohexanol, molecular formula is: C
13h
18br
2n
2o.
The detection method of impurity B of the present invention adopts high performance liquid chromatography to detect, and detection method condition is as follows:
Fixing phase: octadecylsilane chemically bonded silica is filling agent;
Mobile phase: (it is mobile phase that 10% phosphoric acid solution regulates pH value to 7.0) ︰ acetonitrile=(40 ︰ 60) to 0.01mol/L ammonium dibasic phosphate solution;
Detect wavelength: 250nm;
The preparation of each solution:
1) it is appropriate that precision measures sample solution, adds mobile phase and be diluted to debita spissitudo, as need testing solution;
2) precision measures need testing solution 1ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast solution;
3) separately get impurity B reference substance appropriate, accurately weighed, and be diluted to the solution that concentration is about 1 ~ 3 μ g/ml with mobile phase, as impurity B reference substance solution;
Precision measures the appropriate injection liquid chromatography of reference substance solution, makes the peak height of major component chromatographic peak be about 1/5 of full scale; Precision measures need testing solution and impurity B reference substance solution is appropriate, and injection liquid chromatography, records 3 times to major component retention time of chromatogram respectively, records chromatogram.
In detection method of the present invention, the concentration of need testing solution is 150 ~ 500 μ g/ml; Preferably 375 μ g/ml; The concentration of impurity B reference substance solution is 1 ~ 3 μ g/ml, preferably 2 μ g/ml; Each solution need face with now joining.
The detection method of impurity D of the present invention adopts high performance liquid chromatography to detect, and detection method condition is as follows:
Fixing phase: octadecylsilane chemically bonded silica is filling agent;
Mobile phase: (it is mobile phase that 10% phosphoric acid solution regulates pH value to 7.0) ︰ acetonitrile=(40 ︰ 60) to 0.01mol/L ammonium dibasic phosphate solution;
Detect wavelength: 250nm;
The preparation of each solution:
1) it is appropriate that precision measures sample solution, adds mobile phase and be diluted to debita spissitudo, as need testing solution;
2) precision measures need testing solution 1ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shake up,
Solution in contrast;
3) separately get impurity D reference substance appropriate, accurately weighed, and be diluted to the solution that concentration is about 1 ~ 3 μ g/ml with mobile phase, as impurity D reference substance solution;
Precision measures the appropriate injection liquid chromatography of reference substance solution, makes the peak height of major component chromatographic peak be about 1/5 of full scale; Precision measures need testing solution and impurity D reference substance solution is appropriate, and injection liquid chromatography, records 3 times to major component retention time of chromatogram respectively, records chromatogram.
In detection method of the present invention, the concentration of need testing solution is 150 ~ 500 μ g/ml; Preferably 375 μ g/ml; The concentration of impurity D reference substance solution is 1 ~ 3 μ g/ml, preferably 2 μ g/ml; Each solution need face with now joining.
The present invention adopts the detection method of related substance in ambroxol hydrochloride injection by HPLC, specific as follows:
Chromatographic condition: taking octadecylsilane chemically bonded silica as filling agent; Taking 0.01mol/L ammonium dibasic phosphate solution, (10% phosphoric acid solution regulates pH value to 7.0) ︰ acetonitrile=(40 ︰ 60) as mobile phase; Detect wavelength 250nm.
Assay method: it is appropriate that precision measures sample solution, adds mobile phase and is diluted to the need testing solution that concentration is 150 ~ 500 μ g/ml; Precision measures need testing solution 1ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast solution; Separately get impurity B reference substance and impurity D reference substance is appropriate, accurately weighed, be diluted to mobile phase the solution that concentration is about 1 ~ 3 μ g/ml respectively, as impurity B and impurity D reference substance solution.Precision measures contrast solution 20 μ l injection liquid chromatographies, regulates detection sensitivity, makes the peak height of major component chromatographic peak be about 1/5 of registering instrument full scale.(each solution all needs to face with now joining) respectively precision measures the appropriate injection liquid chromatography of need testing solution, contrast solution, impurity B reference substance solution and impurity D reference substance solution, records chromatogram.
The present invention adopts the detection method of five kinds of known impurities in ambroxol hydrochloride injection by HPLC, specific as follows:
Chromatographic condition: taking octadecylsilane chemically bonded silica as filling agent; Taking 0.01mol/L ammonium dibasic phosphate solution, (10% phosphoric acid solution regulates pH value to 7.0) ︰ acetonitrile=(40 ︰ 60) as mobile phase; Detect wavelength 250nm.
Assay method: precision measures injection liquid samples 2ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, and makes the need testing solution that concentration is 150 μ g/ml; Precision measures need testing solution 1ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast solution; Separately get ambroxol hydrochloride known impurities A, B, C, D and E reference substance appropriate, accurately weighed, be diluted to mobile phase the solution that concentration is about 1.5 μ g/ml respectively, as A, B, C, D and E impurity reference substance solution.Precision measures contrast solution 20 μ l injection liquid chromatographies, regulates detection sensitivity, makes the peak height of major component chromatographic peak be about 1/5 of registering instrument full scale.(each solution all needs to face with now joining) respectively precision measures need testing solution, contrast solution, five kinds of appropriate injection liquid chromatographies of impurity reference substance solution, records 3 times to major component retention time of chromatogram.
Brief description of the drawings
Fig. 1 the inventive method is measured the need testing solution liquid chromatogram of impurity B in ambroxol hydrochloride injection;
Fig. 2 the inventive method is measured the reference substance solution liquid chromatogram of impurity B in ambroxol hydrochloride injection;
Fig. 3 the inventive method is measured the need testing solution liquid chromatogram of impurity D in ambroxol hydrochloride injection;
Fig. 4 the inventive method is measured the reference substance solution liquid chromatogram of impurity D in ambroxol hydrochloride injection;
Fig. 5 the inventive method is measured impurity B parting liquid LC-MS collection of illustrative plates in ambroxol hydrochloride injection;
Fig. 6 the inventive method is measured impurity D parting liquid LC-MS collection of illustrative plates in ambroxol hydrochloride injection
Fig. 7 the inventive method is measured ambroxol hydrochloride reference substance solution liquid chromatogram;
Fig. 8 the inventive method is measured ambroxol hydrochloride injection and five kinds of known impurities application of sample solution liquid chromatograms;
Embodiment
The following example is to further explanation of the present invention and explanation, but does not mean that it limits the scope of the invention by any way.
The assay method of related substance in embodiment 1 ambroxol hydrochloride injection of the present invention
Assay method: precision measures injection liquid samples 5ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, and makes the need testing solution that concentration is 375 μ g/ml; Precision measures need testing solution 1ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast solution; Separately get impurity B reference substance and impurity D reference substance is appropriate, accurately weighed, be diluted to mobile phase the solution that concentration is about 2 μ g/ml respectively, as impurity B and impurity D reference substance solution.Precision measures contrast solution 20 μ l injection liquid chromatographies, regulates detection sensitivity, makes the peak height of major component chromatographic peak be about 1/5 of registering instrument full scale.(each solution all needs to face with now joining) respectively precision measures the each 20 μ l injection liquid chromatographies of need testing solution, contrast solution, impurity B reference substance solution and impurity D reference substance solution, records 3 times to major component retention time of chromatogram.Accompanying drawing 1 ~ Fig. 4 is shown in by concrete collection of illustrative plates.
Chromatographic condition: taking octadecylsilane chemically bonded silica as filling agent; Taking 0.01mol/L ammonium dibasic phosphate solution, (10% phosphoric acid solution regulates pH value to 7.0) ︰ acetonitrile=(40 ︰ 60) as mobile phase; Detect wavelength 250nm.
The assay method of related substance in embodiment 2 ambroxol hydrochloride injection of the present invention
Assay method: precision measures injection liquid samples 2ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, and makes the need testing solution that concentration is 150 μ g/ml; Precision measures need testing solution 1ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast solution; Separately get impurity B reference substance and impurity D reference substance is appropriate, accurately weighed, be diluted to mobile phase the solution that concentration is about 1.5 μ g/ml respectively, as impurity B and impurity D reference substance solution.Precision measures contrast solution 20 μ l injection liquid chromatographies, regulates detection sensitivity, makes the peak height of major component chromatographic peak be about 1/5 of registering instrument full scale.(each solution all needs to face with now joining) respectively precision measures the each 20 μ l injection liquid chromatographies of need testing solution, contrast solution, impurity B reference substance solution and impurity D reference substance solution, records 3 times to major component retention time of chromatogram.Accompanying drawing 1 ~ Fig. 4 is shown in by concrete collection of illustrative plates.
Chromatographic condition: taking octadecylsilane chemically bonded silica as filling agent; Taking 0.01mol/L ammonium dibasic phosphate solution, (10% phosphoric acid solution regulates pH value to 7.0) ︰ acetonitrile=(40 ︰ 60) as mobile phase; Detect wavelength 250nm.
Impurity B and impurity D LC-MS detection method in embodiment 3 ambroxol hydrochloride injection of the present invention
Chromatographic condition: fixing phase Luna C18 5u 4.6*150mm
Mobile phase methanol-20mM ammonium acetate=70 ︰ 30
30 DEG C of sample sizes of flow velocity 0.4ml/min column temperature, 10 μ l
UV detecting device wavelength 250nm
Mass spectrum condition: adopt ESI source, positive ion mode, nitrogen 40L/min, assisted gas 10L/min, kapillary
Voltage 4.5KV, 250 DEG C of ion source temperatures, acquisition mode: MS/Full
Instrument: Finnigan surveyor PDA Plus Detector
Finnigan?surveyor?Autosampler?Plus
Finnigan?surveyor?Lc?Pump?Plus
Finnigan?LCQ?Advantage?Max
Assay method: adopt preparation liquid phase to collect respectively impurity B separation solution and impurity D separation solution in ambroxol hydrochloride injection appropriate, be diluted to mobile phase the impurity separation solution that concentration is about 15 μ g/ml respectively, as impurity B and impurity D need testing solution.Precision measures impurity B and impurity D separation solution 10 μ l injection liquid matter combined instruments (LC-MS) (each solution all needs to face with now joining) respectively, records LC-MS spectrogram.Concrete collection of illustrative plates is shown in accompanying drawing 5 and Fig. 6.
Five kinds of known impurities assay methods in embodiment 4 ambroxol hydrochloride injection of the present invention
Liquid phase chromatogram condition:
Instrument: Laballiance series III pump, Spectra100 detecting device, Laballiance HPLC workstation
Chromatographic column: Venusil MP C
184.6mm × 250mm(5 μ)
Mobile phase: 0.01mol/L ammonium dibasic phosphate solution (10% phosphoric acid solution regulates pH value to 7.0): acetonitrile=40:60
Detect wavelength: 250nm
Column temperature: 30 DEG C
Sensitivity: 0.01AUFS
Assay method: precision measures injection liquid samples 2ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, and makes the need testing solution that concentration is 150 μ g/ml; Precision measures need testing solution 1ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast solution; Separately get ambroxol hydrochloride known impurities A, B, C, D and E reference substance appropriate, accurately weighed, be diluted to mobile phase the solution that concentration is about 1.5 μ g/ml respectively, as A, B, C, D and E impurity reference substance solution.Precision measures contrast solution 20 μ l injection liquid chromatographies, regulates detection sensitivity, makes the peak height of major component chromatographic peak be about 1/5 of registering instrument full scale.(each solution all needs to face with now joining) respectively precision measures need testing solution, contrast solution, five kinds of each 20 μ l injection liquid chromatographies of impurity reference substance solution, records 3 times to major component retention time of chromatogram.Concrete collection of illustrative plates is shown in accompanying drawing 7 and Fig. 8.
Claims (12)
1. the detection method of ambroxol hydrochloride injection impurity, is characterized in that: described impurity is impurity D, and its chemical name is cis-4-[(2-amino-3,5-dibromobenzene methyl) amino] cyclohexanol;
Adopt high performance liquid chromatography, its chromatographic condition is: octadecylsilane chemically bonded silica is filling agent, 0.01mol/L ammonium dibasic phosphate solution: acetonitrile=(40:60) is mobile phase, and detection wavelength is 250nm.
2. method according to claim 1, wherein ammonium dibasic phosphate solution is that 0.01mol/L diammonium hydrogen phosphate 10% phosphoric acid solution regulates pH to 7.0 and makes.
3. method according to claim 1 and 2, wherein the concentration of need testing solution is 150 ~ 500 μ g/mL; Preferably 375 μ g/mL; The concentration of impurity reference substance solution is 1 ~ 3 μ g/mL, preferably 2 μ g/mL; The volume of need testing solution and impurity reference substance solution injection liquid chromatography is 20 μ l; Each solution all faces with newly joining.
4. method according to claim 1 and 2, wherein, described method comprises the following steps:
Measure according to the high performance liquid chromatography in Chinese Pharmacopoeia;
Regulator solution chromatography detection sensitivity; Precision measures need testing solution and the each 20 μ l of impurity D reference substance solution, and injection liquid chromatography, records 3 times to major component retention time of chromatogram respectively.
5. an associated detecting method of impurity B and impurity D, is characterized in that: the chemical name of described impurity B is trans-4-[6, bromo-Isosorbide-5-Nitrae-dihydroquinazoline-3 of 8-bis-(2H)] cyclohexanol; Adopt high performance liquid chromatography, its chromatographic condition is: octadecylsilane chemically bonded silica is filling agent, 0.01mol/L ammonium dibasic phosphate solution: acetonitrile=(40:60) is mobile phase, and detection wavelength is 250nm.
6. method according to claim 5, wherein ammonium dibasic phosphate solution is that 0.01mol/L diammonium hydrogen phosphate 10% phosphoric acid solution regulates pH to 7.0 and makes.
7. according to the method described in claim 5 or 6, wherein the concentration of need testing solution is 150 ~ 500 μ g/mL; Preferably 375 μ g/mL; The concentration of impurity B and impurity D reference substance solution is 1 ~ 3 μ g/mL, preferably 2 μ g/mL; The volume of need testing solution and impurity B and impurity D reference substance solution injection liquid chromatography is 20 μ l; Each solution all faces with newly joining.
8. according to the method described in claim 5 or 6, wherein, described method comprises the following steps:
Measure according to the high performance liquid chromatography in Chinese Pharmacopoeia;
Regulator solution chromatography detection sensitivity; Precision measures the each 20 μ l injection liquid chromatographies of need testing solution, contrast solution, impurity B reference substance solution and impurity D reference substance solution respectively, records 3 times to major component retention time of chromatogram.
9. the detection method of ambroxol hydrochloride injection impurity, is characterized in that, described impurity comprises impurity A, B, C, D and E;
Adopt high performance liquid chromatography, its chromatographic condition is: octadecylsilane chemically bonded silica is filling agent, 0.01mol/L ammonium dibasic phosphate solution: acetonitrile=(40:60) is mobile phase, and detection wavelength is 250nm.
10. method according to claim 9, wherein ammonium dibasic phosphate solution is that 0.01mol/L diammonium hydrogen phosphate 10% phosphoric acid solution regulates pH to 7.0 and makes.
11. according to the method described in claim 9 or 10, and wherein the concentration of need testing solution is 150 ~ 500 μ g/mL; Preferably 375 μ g/mL; The concentration of impurity reference substance solution is 1 ~ 3 μ g/mL, preferably 2 μ g/mL; The volume of need testing solution and impurity reference substance solution injection liquid chromatography is 20 μ l; Each solution all faces with newly joining.
12. according to the method described in claim 9 or 10, and wherein, described method comprises the following steps:
Measure according to the high performance liquid chromatography in Chinese Pharmacopoeia;
Regulator solution chromatography detection sensitivity; Precision measures need testing solution, contrast solution, five kinds of each 20 μ l injection liquid chromatographies of impurity reference substance solution respectively, records 3 times to major component retention time of chromatogram.
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| CN113533578A (en) * | 2021-07-29 | 2021-10-22 | 地奥集团成都药业股份有限公司 | Quality control method of related substances in bromhexine hydrochloride tablets |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104316482A (en) * | 2014-08-15 | 2015-01-28 | 河北菲尼斯生物技术有限公司 | A quality control method for ambroxol hydrochloride particles |
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| CN106950291A (en) * | 2016-12-31 | 2017-07-14 | 辰欣药业股份有限公司 | A kind of detection method of ambroxol hydrochloride injection about material |
| CN113049687A (en) * | 2019-12-27 | 2021-06-29 | 石药集团欧意药业有限公司 | Method for detecting related substances of ambroxol hydrochloride raw material and injection |
| 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 |
| CN113533578A (en) * | 2021-07-29 | 2021-10-22 | 地奥集团成都药业股份有限公司 | Quality control method of related substances in bromhexine hydrochloride tablets |
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