CN102636600A - Method for determination of optical isomers in palonosetron hydrochloride composition - Google Patents
Method for determination of optical isomers in palonosetron hydrochloride composition Download PDFInfo
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- CN102636600A CN102636600A CN2012101366069A CN201210136606A CN102636600A CN 102636600 A CN102636600 A CN 102636600A CN 2012101366069 A CN2012101366069 A CN 2012101366069A CN 201210136606 A CN201210136606 A CN 201210136606A CN 102636600 A CN102636600 A CN 102636600A
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- palonosetron
- palonosetron hydrochloride
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- diethylamine
- ethyl alcohol
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Abstract
The invention provides a method for detecting palonosetron hydrochloride isomers in a palonosetron hydrochloride composition. The method adopts a chiral chromatographic column with amylose tris(3,5-dimethylphenylcarbamate) as filler; n-hexane/absolute ethyl alcohol /diethylamine as a mobile phase; and a detection wavelength of 240nm. The method comprises the following steps of preparing 0.5mug/ml of a solution containing palonosetron hydrochloride isomers with the mobile phase as a reference solution, performing determination and recording the spectra. The method provided by the invention can effectively separate three optical isomers of palonosetron hydrochloride under the same chromatographic conditions, and the separation degree between palonosetron hydrochloride and each of the isomers of palonosetron hydrochloride can be up to 1.5 to 2.0, which is in line with the requirements of Chinese Pharmacopoeia. The method provided by the invention can also be used for quantitative determination of palonosetron hydrochloride isomers.
Description
Technical field
The invention belongs to field of medicaments, more specifically relate to a kind of method that detects palonosetron Hcl isomeride in the palonosetron Hcl composition.
Background technology
Palonosetron Hcl (Palonosetron Hydrochloride) chemical structural formula is:
Chemical name is: 2-[1-azabicyclo (2.2.2) suffering-3S-yl]-2,3,3aS, 4,5,6-six hydrogen-1H-benzo [de] isoquinoline-1-keto hydrochloride.
Palonosetron Hcl is the 5-hydroxytryptamine receptor antagonist that Switzerland Helsinn Healthine company develops; Be white or off-white powder; These article are very easily dissolving in 0.1mol/L hydrochloric acid solution and water; In methyl alcohol, dissolve, soluble,very slightly in ethanol, almost insoluble in the 0.1mol/L sodium hydroxide solution.Its parenteral solution in September, 2003 in U.S.'s list marketing, commodity are called Aloxi
Vomiting reaction when being mainly used in treatment cancer chemotherapy, radiotherapy clinically; The main ingredient toxic and side effect is little, and the biology phase of declining is grown (about 40h) in vivo, and is obvious to the inhibiting effect of period of delay vomiting, is a kind of antemetic of safe, effective, persistent.
Two chiral centers are arranged in the palonosetron Hcl structural formula, have three optical isomers, be respectively R, R type isomeride, S, R type isomeride, R, S type isomeride.Detection method of the prior art; Chromatographic condition among the Chinese patent ZL200710074410.0 (notification number CN101303331B) can only be controlled enantiomter; And two other diastereo-isomerism can't be detected simultaneously, need to use two different chromatographic conditions to measure respectively.When one of them diastereo-isomerism was measured, the another one diastereo-isomerism was known from experience with main peak overlapping, accurately measured influential to the content of impurity.Be strictness control product quality,, set up the chromatographic condition that can detect palonosetron Hcl in the palonosetron Hcl composition and RR type isomeride thereof, RS type isomeride, SR type isomeride simultaneously through research.
Summary of the invention
The present invention is directed to the deficiency of prior art, provide a kind of under same chromatographic condition, detect a kind of enantiomter of palonosetron Hcl in the palonosetron Hcl composition and the method for two kinds of diastereo-isomerisms simultaneously.
The purpose of this invention is to provide the R that detects palonosetron Hcl in the palonosetron Hcl composition through high performance liquid chromatography; R type isomeride, S; R type isomeride, R, S type content of isomer, the product quality of the palonosetron Hcl composition that assurance is produced.
The method of the palonosetron hydrochloride optical isomer in the detection palonosetron Hcl composition according to the invention; Be with three (3; 5-3,5-dimethylphenyl carbamate) amylose is the chiral chromatographic column of filling agent; Moving phase is that normal hexane-absolute ethyl alcohol-diethylamine detects, and the detection wavelength is 240nm, and column temperature is 20 ℃.
Wherein the volume ratio of moving phase normal hexane, absolute ethyl alcohol and diethylamine is 90 ~ 95:5 ~ 10:0.1 ~ 0.5; Preferred 93:7:0.2.Wherein flow velocity is 0.5 ~ 0.8ml/min, preferred 0.6ml/min.
The preparation of sample solution is following among the present invention:
(1), need testing solution: get 10 of palonosetron Hcl compositions, put in the evaporating dish, in water-bath, be concentrated into about 5ml; Put coldly, add ethanol 40ml, mixing makes deposition fully; Filter, get the filtrating evaporate to dryness, residue is transferred to the 25ml measuring bottle after with an amount of dissolve with ethanol; Be diluted to scale with moving phase, shake up, as need testing solution;
(2), reference substance solution: precision takes by weighing R respectively; R type palonosetron reference substance, S, R type palonosetron reference substance and R, S type palonosetron reference substance is an amount of; Add moving phase quantitatively dilution process that each contains the mixed solution of 0.5 μ g approximately among every 1ml, as reference substance solution.
Measure: precision is measured need testing solution and each 100 μ l of reference substance solution; Inject liquid chromatograph respectively; The record chromatogram, in the chromatogram of need testing solution if any with contrast solution in the chromatographic peak of the corresponding retention time of isomeride, calculate the content of isomeride by external standard method.
Adopting this chromatographic condition under a chromatographic condition, to measure simultaneously in the palonosetron Hcl composition is the content of three kinds of optical isomers, and palonosetron Hcl and each isomeride degree of separation are 1.5 ~ 2.0, meet the Chinese Pharmacopoeia requirement.Simultaneously, this chromatographic condition can be used for the quantitative of palonosetron Hcl isomeride.With prior art need be under different chromatographic conditions respectively method for measuring compare, it is high to measure result precision, easier, preferablyly in drug production process, uses.
Description of drawings
Fig. 1 palonosetron Hcl and isomer separation figure thereof (A peak: R, R type palonosetron; B peak: R, S type palonosetron; C peak: S, S type palonosetron; D:S, R type palonosetron).
Fig. 2 embodiment 3 palonosetron Hcl composition (100501) isomeride testing results (A peak: S, S type palonosetron).
Embodiment
Embodiment 1
Instrument: LC-10AT high performance liquid chromatograph system in Tianjin, island comprises the LC-10AT pump, SPD-10A UV-detector and HW chromatographic work station.
Chromatographic column: chiral chromatographic column Chiralpak ADH post (250mm * 4.6mm, 5 μ m).
Moving phase: normal hexane-absolute ethyl alcohol-diethylamine (93:7:0.2)
Detect wavelength: 240nm
Flow velocity: 0.6 ml/min
Column temperature: 20 ℃
Reference substance solution: precision takes by weighing R respectively; R type palonosetron reference substance, S, R type palonosetron reference substance and R, S type palonosetron reference substance is an amount of; Add moving phase quantitatively dilution process that each contains the mixed solution of 0.5 μ g approximately among every 1ml, as reference substance solution.
Need testing solution: get 10 of palonosetron Hcl compositions, put in the evaporating dish, in water-bath, be concentrated into about 5ml; Put coldly, add ethanol 40ml, mixing makes deposition fully; Filter, get the filtrating evaporate to dryness, residue is transferred to the 25ml measuring bottle after with an amount of dissolve with ethanol; Be diluted to scale with moving phase, shake up, as need testing solution.
Measure: precision is measured need testing solution and each 100 μ l of reference substance solution, injects liquid chromatograph respectively, the record chromatogram.In the chromatogram of need testing solution if any with contrast solution in the chromatographic peak of the corresponding retention time of isomeride, calculate the content of isomeride by external standard method.
Embodiment 2 measures used palonosetron Hcl preparation method of composition
Prescription:
Palonosetron Hcl 0.28g
Sweet mellow wine 207.5g
Edetate sodium 0.5g
Citric acid 25g
Water for injection 5000ml
Process 1000
Take by weighing sweet mellow wine, edetate sodium and the citric acid of recipe quantity, be added in 96% the water for injection, stirring and dissolving adds the 0.1mol/L sodium hydroxide solution; Adjust pH about 5.0 (4.5～5.5) adds 0.1% needle-use activated carbon, in 80 ℃ of stirrings 30 minutes, takes off charcoal while hot with the titanium alloy rod; The palonosetron Hcl that adds recipe quantity then after the stirring and dissolving, is mended water for injection to full dose, and is extremely clear and bright through 0.22 μ m filtering with microporous membrane again; Measure intermedium content and pH value, qualified after, press every bottle of 5ml can in ampoule, seal; 121 ℃ of pressure sterilizings of warp 15 minutes, quality inspection, packing promptly gets.
Embodiment 3
Prepare three batches of palonosetron Hcl composition sample and detect palonosetron Hcl content of isomer in every batch of composition by embodiment 2, concrete outcome is seen table 1.
Palonosetron Hcl isomeride check result in the table 1 palonosetron Hcl composition
| Lot number | RR type isomeride | RS type isomeride | SR type isomeride |
| 100501 | Do not detect | Do not detect | Do not detect |
| 100502 | Do not detect | Do not detect | Do not detect |
| 100503 | Do not detect | Do not detect | Do not detect |
Claims (5)
1. method that detects the palonosetron hydrochloride optical isomer in the palonosetron Hcl composition; Be with three (3; 5-3,5-dimethylphenyl carbamate) amylose is the chiral chromatographic column of filling agent; Moving phase is that normal hexane-absolute ethyl alcohol-diethylamine detects, and it is characterized in that detecting wavelength is 240nm, and column temperature is 20 ℃.
2. method according to claim 1, the volume ratio that it is characterized in that normal hexane, absolute ethyl alcohol and diethylamine is 90 ~ 95:5 ~ 10:0.1 ~ 0.5.
3. method according to claim 2, the volume ratio that it is characterized in that normal hexane, absolute ethyl alcohol and diethylamine is 93:7:0.2.
4. method according to claim 1 is characterized in that flow velocity is 0.6ml/min.
5. according to the described method of one of claim 1 ~ 4, it is characterized in that the palonosetron Hcl composition is concentrated into 5ml earlier, add ethanol; After will precipitating filtering; The evaporate to dryness of will filtrating is transferred to the 25ml measuring bottle with ethanol after with the residue dissolving again, is diluted to scale with moving phase; Hydrochloric palonosetron 0.1mg/ml is as need testing solution.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107328880A (en) * | 2017-08-09 | 2017-11-07 | 杭州新博思生物医药有限公司 | A kind of method of reversed phase chromatography separation palonosetron hydrochloride for injection about material |
| CN107870211A (en) * | 2016-09-28 | 2018-04-03 | 南京先声东元制药有限公司 | A kind of liquid-phase chromatography method of separation determination palonosetron Hcl |
| CN109239231A (en) * | 2018-10-31 | 2019-01-18 | 药源生物科技（启东）有限公司 | A kind of chiral isomer analysis method |
| CN114324638A (en) * | 2021-12-21 | 2022-04-12 | 重庆华邦胜凯制药有限公司 | Method for simultaneously separating and determining palonosetron hydrochloride and impurities thereof |
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| US20080058367A1 (en) * | 2006-08-30 | 2008-03-06 | Palle Raghavendracharyulu Venk | Process for the purification of palonosetron or its salt |
| CN101303331A (en) * | 2007-05-11 | 2008-11-12 | 深圳万乐药业有限公司 | Method for separating and measuring palonosetron hydrochloride optical isomer |
| WO2009136405A1 (en) * | 2008-05-05 | 2009-11-12 | Natco Pharma Limited | High purity palonosetron base and its solid state characteristics |
| CN102207494A (en) * | 2010-03-31 | 2011-10-05 | 深圳海王药业有限公司 | Method for simultaneously determining four optical isomers of palonosetron hydrochloride |
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2012
- 2012-05-06 CN CN201210136606.9A patent/CN102636600B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20080058367A1 (en) * | 2006-08-30 | 2008-03-06 | Palle Raghavendracharyulu Venk | Process for the purification of palonosetron or its salt |
| CN101303331A (en) * | 2007-05-11 | 2008-11-12 | 深圳万乐药业有限公司 | Method for separating and measuring palonosetron hydrochloride optical isomer |
| WO2009136405A1 (en) * | 2008-05-05 | 2009-11-12 | Natco Pharma Limited | High purity palonosetron base and its solid state characteristics |
| CN102207494A (en) * | 2010-03-31 | 2011-10-05 | 深圳海王药业有限公司 | Method for simultaneously determining four optical isomers of palonosetron hydrochloride |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107870211A (en) * | 2016-09-28 | 2018-04-03 | 南京先声东元制药有限公司 | A kind of liquid-phase chromatography method of separation determination palonosetron Hcl |
| CN107328880A (en) * | 2017-08-09 | 2017-11-07 | 杭州新博思生物医药有限公司 | A kind of method of reversed phase chromatography separation palonosetron hydrochloride for injection about material |
| CN107328880B (en) * | 2017-08-09 | 2019-11-22 | 杭州新博思生物医药有限公司 | A kind of method of the reversed phase chromatography separation palonosetron hydrochloride for injection in relation to substance |
| CN109239231A (en) * | 2018-10-31 | 2019-01-18 | 药源生物科技（启东）有限公司 | A kind of chiral isomer analysis method |
| CN114324638A (en) * | 2021-12-21 | 2022-04-12 | 重庆华邦胜凯制药有限公司 | Method for simultaneously separating and determining palonosetron hydrochloride and impurities thereof |
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Inventor after: Chen Qingcai Inventor after: Chen Xiangfeng Inventor after: Ren Feng Inventor after: Yang Qizhen Inventor before: Ren Feng Inventor before: Yang Qizhen |
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Address after: 211112 Kejian Road, Jiangning Science Park, Nanjing City, Jiangsu Province, 699 Patentee after: Jiangsu Aosaikang Pharmaceutical Co., Ltd. Address before: 211112 Kejian Road, Jiangning Science Park, Nanjing City, Jiangsu Province, 699 Patentee before: Jiangsu Aosaikang Pharmaceutical Co., Ltd. |
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