CN104634887A - Method for separating and measuring ticagrelor and optical isomer of ticagrelor - Google Patents
Method for separating and measuring ticagrelor and optical isomer of ticagrelor Download PDFInfo
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- CN104634887A CN104634887A CN201410614624.2A CN201410614624A CN104634887A CN 104634887 A CN104634887 A CN 104634887A CN 201410614624 A CN201410614624 A CN 201410614624A CN 104634887 A CN104634887 A CN 104634887A
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Abstract
The invention belongs to the field of analytical chemistry and in particular relates to a method for separating and measuring ticagrelor and a diastereoisomer of the ticagrelor. The method is characterized in that a chiral HPLC (High Performance Liquid Chromatography) column taking polysaccharide derivative as a filler is used and a mixed solution of lower paraffin hydrocarbon and low alcohol is used as a moving phase; according to the separating and detecting method, the ticagrelor and the diastereoisomer of the ticagrelor are effectively separated, and the mass of the ticagrelor can be effectively controlled. The method can be used for separating and detecting the ticagrelor and the diastereoisomer of the ticagrelor simply, rapidly and accurately.
Description
Technical field
The present invention relates to analytical chemistry field, be specifically related to the method with liquid phase chromatography separated island form ticagrelor and diastereo-isomerism thereof.
Background technology
Ticagrelor (Ticagrelor), chemical name is (1S, 2S, 3R, 5S)-3-(7-((1R, 2S)-2-(3,4-difluorophenyl) cyclopropyl amino)-5-(rosickyite base)-3H-[1,2,3] triazole [4,5-d] pyrimidin-3-yl)-5-(2-hydroxyl-oxethyl) cyclopentane-1,2-glycol), its chemical constitution is such as formula shown in (I)
Ticagrelor is a kind of novel cyclopentyl triazolo pyrimidine class (CPTP) the oral antidiabetic aggregation medicinal researched and developed by AstraZeneca (AstraZeneca) company, can be combined with P2Y adp receptor reversibility, obvious inhibiting effect is had to the platelet aggregation of ADP mediation, the incidence of the angiocardiopathies such as heart disease can be reduced, and reduce the mortality ratio of Acute Coronary Syndrome Patients.
(1R, 2S)-2-(3,4-difluorophenyl) cyclopropylamine, shown in (II), is the starting material of synthesis ticagrelor, there are 2 chiral centers, containing an enantiomter impurity,
An optical isomer can be introduced by the enantiomter impurity in Compound II per in the chemosynthesis carrying out ticagrelor, i.e. diastereo-isomerism, wherein diastereo-isomerism chemical name is: (1S, 2S, 3R, 5S)-3-(7-((1S, 2R)-2-(3, 4-difluorophenyl) cyclopropyl amino)-5-(rosickyite base)-3H-[1, 2, 3] triazole [4, 5-d] pyrimidin-3-yl)-5-(2-hydroxyl-oxethyl) cyclopentane-1, 2-glycol (hereinafter referred diastereo-isomerism), this diastereo-isomerism ubiquity in the sample to which, be listed in the impurity of ticagrelor, affect the quality of ticagrelor bulk drug and formulation products thereof, need in process of production to carry out strict quality control to it.At present, " American Pharmacopeia " USP, " European Pharmacopoeia " EP and " Chinese Pharmacopoeia " Ch.P all do not record the analytical approach of ticagrelor diastereo-isomerism, do not retrieve the method for separating and detecting of related documents report ticagrelor and diastereo-isomerism thereof yet.
Summary of the invention
Term definition
Term " approximately " or " about "
In content hereafter or hereafter, no matter whether use the wording such as " approximately " or " about ", all numerals disclosed at this are approximate value.The numerical value of each numeral likely there will be the difference such as 1%, 2%, 5%, 7%, 8%, 10%, 15% or 20%.Whenever disclosing one and having N value digital, any have N+/-1%, N+/-2%, N+/-3%, N+/-5%, N+/-7%, N+/-8%, N+/-10%, and the numeral of N+/-15%or N+/-20% value can be specifically disclosed, and wherein " +/-" refers to and add deduct.Whenever disclosing a lower limit in a numerical range, RL, and a upper limit, RU, time, the numerical value within any scope being in the disclosed can be specifically disclosed.Particularly, contain the following numerical value within the scope of this: R=RL+K* (RU-RL), wherein k be one by 1% increment increase from 1% to 100% variable.As: 1%, 2%, 3%, 4%, 5%...50%, 51%, 52%...95%, 96%, 97%, 98%, 99% or 100%.In addition, also contain especially this disclose above-mentioned with the numerical range of two R definition.
Detailed Description Of The Invention
In order to control the content of diastereo-isomerism in product more accurately, ensure the quality of bulk drug and formulation products, the present inventor, through repetition test and research, develops the analytical approach being suitable for ticagrelor and diastereo-isomerism assay thereof.Method of the present invention can simply, quickly and accurately be separated, detect ticagrelor and diastereo-isomerism thereof.
The object of the present invention is to provide a kind of method of liquid chromatography for separating and determining ticagrelor and diastereo-isomerism impurity thereof, thus realize the separated island form of ticagrelor and diastereo-isomerism impurity thereof.
Apply a method for liquid chromatography for separating and determining ticagrelor and diastereo-isomerism thereof, it is characterized in that, adopting with polysaccharide derivates is the chiral chromatographic column of filler, with the mixed solution of lower paraffin hydrocarbon and lower alcohol for mobile phase.
In certain embodiments, the polysaccharide derivates filler of described chiral chromatographic column is amylose-three (3,5-xylyl carbamate), amylose-three [(S)-α-tolylcarbamate], cellulose-three (3,5-xylyl carbamate), cellulose-three [4-methyl benzoic acid ester], cellulose-three (3,5-dichlorophenyl carbamate) or its combination, in certain embodiments, polysaccharide derivates filler is amylose-three (3,5-xylyl carbamate).
In certain embodiments, described chiral chromatographic column is CHIRALPAK AD, CHIRALPAK AS-H, CHIRALCEL OD-H, CHIRALCEL OJ-H or CHIRALPAK IC, CHIRALPAK AD-H, selling producer is Daicel medicine chiral technology (Shanghai) Co., Ltd., English name DAICEL CHIRAL TECHNOLOGIES (CHINA) CO., LTD.
In certain embodiments, described lower paraffin hydrocarbon is the alkane of C6-C8, is selected from normal hexane, normal heptane, cyclohexane or its combination in certain embodiments.
In certain embodiments, described lower alcohol is the alcohol of C1-C4, is selected from methyl alcohol, ethanol, propyl alcohol, normal butyl alcohol, isopropyl alcohol or its combination in certain embodiments, and being ethanol, isopropyl alcohol or its combination in certain embodiments, is ethanol in certain embodiments.
In certain embodiments, in described lower alcohol, organic acid can be contained further, in further embodiments, the potpourri of organic acid and organic amine in described lower alcohol, can be contained.
Described organic acid is selected from formic acid, acetic acid and trifluoroacetic acid, and the percent by volume that organic acid concentration (V/V) accounts for lower alcohol is about 0.05% to about 10%.
In certain embodiments, the volume ratio (V/V) of described mobile phase lower paraffin hydrocarbon and low-alcohol solution is 5:5 to 9:1, or is 6:4 to 9:1, or is 7:3 to 9:1, or is 8:2.
Method of separating and assaying of the present invention, comprises following steps:
1) ticagrelor or the formulation samples containing the ticagrelor of any optical purity of getting any optical purity are appropriate, with the mixed solvent of a certain amount of alkanes and alcohols as thinning agent sample dissolution;
2) instrument parameter is set: the post case temperature of the flow velocity of mobile phase, determined wavelength, chromatographic column;
3) get a certain amount of step 1) solution, inject high performance liquid chromatograph, complete the separation determination of ticagrelor and diastereo-isomerism.
Step 1) described in ticagrelor can be any optical purity, the ticagrelor used as bulk drug (API) can adopt the method disclosed in PCT application WO 2010030224 to prepare, the preparation of the potpourri of ticagrelor and its diastereo-isomerism adopts the cyclopropylamine hydrochloride of racemization to be raw material, according to method preparation disclosed in PCT application WO 2010030224; Formulation samples such as ticagrelor ordinary tablet containing ticagrelor is bought from ASTRAZENECA.
Step 1) described in lower alkyl hydro carbons be normal hexane, normal heptane, cyclohexane or its combination; In certain embodiments, described lower alkyl hydro carbons is normal heptane; Described alcohols is methyl alcohol, ethanol, n-propanol, normal butyl alcohol, isopropyl alcohol or its combination, and in certain embodiments, described alcohols is ethanol; In certain embodiments, described mixed solvent is the mixed solvent of normal heptane and ethanol; The volume ratio (V/V) of the alkane solvents in described mixed solvent and alcohols solvent is 45:55 to 90:10; In certain embodiments, the volume ratio (V/V) of the alkane solvents in described mixed solvent and alcohols solvent is 80:20.
In certain embodiments, step 1) described in thinning agent in every 1ml thinning agent containing ticagrelor sample 0.5mg to 5mg; In further embodiments, step 1) described in thinning agent in every 1ml thinning agent containing ticagrelor sample 1mg to 3mg; In certain embodiments, step 1) described in thinning agent in every 1ml thinning agent containing ticagrelor sample 2mg.
Step 2) flow velocity of described mobile phase is 0.3ml/min to 2ml/min, in certain embodiments, the flow velocity of mobile phase is 0.8ml/min; Described determined wavelength is 220nm to 300nm, and in certain embodiments, determined wavelength is 256nm; Described chromatographic column post case temperature is 20 DEG C to 40 DEG C, and in certain embodiments, chromatographic column post case temperature is 30 DEG C.
Step 3) described sample solution sample size is 2 μ l ~ 20 μ l, in certain embodiments, described sample solution sample size is 5 μ l.
Method of separating and assaying of the present invention, comprises following steps:
1) get the potpourri of ticagrelor and diastereomer or ticagrelor or the formulation samples containing ticagrelor appropriate, by the mixed solvent sample dissolution of alkane solvents with alcohols solvent, and be mixed with the sample solution that every 1ml contains ticagrelor 0.5mg to 5mg;
2) flow velocity arranging mobile phase is 0.3ml/min to 2ml/min, and the flow velocity of mobile phase is preferably 0.8ml/min, and determined wavelength is 220nm to 300nm, and determined wavelength is preferably 256nm, and chromatographic column post case temperature is 20 DEG C to 40 DEG C;
3) get step 1) sample solution 2 μ l to 20 μ l, inject high performance liquid chromatograph, complete the separation determination of ticagrelor and diastereomer thereof.
Wherein:
The high performance liquid chromatograph adopted is U.S. Agilent 1260 type highly effective liquid phase chromatographic system and workstation,
Chiral chromatographic column is selected from CHIRALPAK AD-H.
In certain embodiments, mobile phase is the volume ratio (V/V) of normal heptane and ethanol (containing 0.1% trifluoroacetic acid) is 800:200.
It take polysaccharide derivates as the chiral chromatographic column of filler that the present invention adopts, and with the mixed solution of lower paraffin hydrocarbon and lower alcohol for mobile phase, ticagrelor effectively can be separated with its diastereo-isomerism, thus can the quality of accurate and effective control ticagrelor.Adopt separation method of the present invention, method of the present invention can be separated simply, fast and accurately and detect ticagrelor and optical isomer thereof within 35 minutes the time of detection ticagrelor and diastereomer thereof that is separated.
Accompanying drawing explanation
The high-efficient liquid phase chromatogram of Fig. 1 blank solvent;
Fig. 2 shows that embodiment 1 is separated the high-efficient liquid phase chromatogram detected;
Fig. 3 shows that embodiment 2 is separated the high-efficient liquid phase chromatogram detected;
Fig. 4 shows that embodiment 3 is separated the high-efficient liquid phase chromatogram detected.
Embodiment
In order to make those skilled in the art understand technical scheme of the present invention better, below disclose further some non-limiting embodiments the present invention is described in further detail.
Reagent used in the present invention all can be buied from the market or can be obtained by method described in the invention preparation.
In the present invention, mmol represents mM, and h represents hour, and g represents gram, and ml represents milliliter.
The instrument used in the present invention and the specification of chromatographic column are:
U.S. Agilent 1260 type highly effective liquid phase chromatographic system and workstation; Auto injection;
Embodiment 1-embodiment 3: be separated the method detecting ticagrelor and diastereo-isomerism thereof with CHIRALPAK AD-H chiral chromatographic column.
Embodiment 1
Conditional parameter
UV detect wavelength: 256nm; Mobile phase: normal heptane: ethanolic solution (containing 0.1% trifluoroacetic acid) (80ml:20ml) is mobile phase; Column temperature: 30 DEG C; Sampling volume is 5 μ l.
Experimental procedure
Thinning agent: normal heptane: ethanol=80ml:20ml; The potpourri getting ticagrelor and diastereo-isomerism is about 20mg, puts in 10ml measuring bottle, adds 2ml ethanol and dissolves, be then diluted to scale with normal heptane, shake up, as need testing solution.
Get thinning agent (as blank solution) and need testing solution respectively, carry out efficient liquid phase chromatographic analysis by above-mentioned condition, record chromatogram, the results are shown in Figure 1, Fig. 2.In Fig. 2, retention time is the chromatographic peak of 20.987 minutes is the chromatographic peak of ticagrelor; The chromatographic column of 25.727 minutes is the chromatographic peak of the diastereo-isomerism of ticagrelor.
Embodiment 2
Get ticagrelor and be about 20mg, put in 10ml measuring bottle, add 2ml ethanol and dissolve, be then diluted to scale with normal heptane, shake up, as need testing solution.
Get need testing solution, according to the facts the condition of example 1 carries out efficient liquid phase chromatographic analysis, and record chromatogram, the results are shown in Figure 3, wherein, retention time be 20.720 minutes for ticagrelor.Fig. 3 proves, ticagrelor reaches bulk drug requirement, and this law may be used for the quality monitoring of ticagrelor.
Embodiment 3
Get ticagrelor sheet, after being milled into powder, adding 9ml ethanol and dissolve, shake up, filter, get 2ml filtrate in 10ml measuring bottle, be diluted to scale with normal heptane, be mixed with the need testing solution that concentration is about 2mg/ml.
Get need testing solution, according to the facts the condition of example 1 carries out efficient liquid phase chromatographic analysis, and record chromatogram, the results are shown in Figure 4, wherein, retention time be 20.920 minutes for ticagrelor.
Method of the present invention is described by preferred embodiment, and related personnel obviously can change methods and applications as herein described or suitably change and combination in content of the present invention, spirit and scope, realizes and applies the technology of the present invention.Those skilled in the art can use for reference present disclosure, and suitable improving technique parameter realizes.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, they are all deemed to be included in the present invention.
Claims (11)
1. the method with liquid chromatography for separating and determining ticagrelor and diastereo-isomerism thereof, it is characterized in that, adopt the chiral chromatographic column that is filler with amylose-three (3,5-xylyl carbamate), with the mixed solution of lower paraffin hydrocarbon and lower alcohol for mobile phase.
2. method according to claim 1, the volume ratio of lower paraffin hydrocarbon and lower alcohol is 5:5 to 9:1, or is 6:4 to 9:1, or is 7:3 to 9:1, or is 8:2.
3. method according to claim 1 and 2, described lower paraffin hydrocarbon is the alkane of C6-C8, or described lower paraffin hydrocarbon is selected from normal hexane, normal heptane, cyclohexane or its combination.
4. method according to claim 1 and 2, described lower alcohol is the alcohol of C1-C4, or described lower alcohol is selected from methyl alcohol, ethanol, propyl alcohol, normal butyl alcohol, isopropyl alcohol or its combination.
5. method according to claim 4, can contain the potpourri of organic acid or organic acid and organic amine further in described lower alcohol.
6. method according to claim 5, the percent by volume that described organic acid concentration (V/V) accounts for lower alcohol is about 0.05% to about 10%.
7. method according to claim 1, comprises following steps:
1) ticagrelor or the formulation samples containing the ticagrelor of any optical purity of getting any optical purity are appropriate, with the mixed solvent of lower paraffin hydrocarbon and alcohols as thinning agent sample dissolution;
2) instrument parameter is set: the post case temperature of the flow velocity of mobile phase, determined wavelength, chromatographic column;
3) get step 1) solution, inject high performance liquid chromatograph, complete the separation determination of ticagrelor and diastereo-isomerism.
8. method according to claim 7, step 1) described in lower alkyl hydro carbons be normal hexane, normal heptane, cyclohexane or its combination; Step 1) described in alcohols be methyl alcohol, ethanol, n-propanol, normal butyl alcohol, isopropyl alcohol or its combination.
9. method according to claim 7, step 1) described in the mixed solvent of lower alkyl hydro carbons and alcohols be the mixed solvent of normal heptane and ethanol.
10. method according to claim 8 or claim 9, step 1) described in the volume ratio (V/V) of mixed solvent of lower alkyl hydro carbons and alcohols be 45:55 to 90:10, or be 80:20.
11. methods according to claim 7, step 2) described in the flow velocity of mobile phase be 0.3ml/min to 2ml/min, or the flow velocity of mobile phase is 0.8ml/min; Determined wavelength is 220nm to 300nm, or determined wavelength is 256nm; Chromatographic column post case temperature is 20 DEG C to 40 DEG C.
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105301135A (en) * | 2015-11-20 | 2016-02-03 | 扬子江药业集团有限公司 | Method for detecting chiral isomer content of ticagrelor by high performance liquid chromatography |
| CN105510482A (en) * | 2016-01-29 | 2016-04-20 | 成都百裕制药股份有限公司 | Method for detecting content of isomer impurity in raw material for ticagrelor |
| CN105699524A (en) * | 2016-01-29 | 2016-06-22 | 成都百裕制药股份有限公司 | Detection method for content of isomer impurities in Ticagrelor |
| CN106243108A (en) * | 2015-06-03 | 2016-12-21 | 四川海思科制药有限公司 | A kind of highly purified ticagrelor and preparation method thereof |
| CN106645528A (en) * | 2016-11-25 | 2017-05-10 | 成都欣捷高新技术开发股份有限公司 | High performance liquid chromatography detection method of content of chiral isomers of ticagrelor |
| CN106841413A (en) * | 2015-12-04 | 2017-06-13 | 江苏恒瑞医药股份有限公司 | A kind of ticagrelor enantiomter, the method for separating and detecting of diastereoisomer |
| CN109387578A (en) * | 2017-08-11 | 2019-02-26 | 四川海思科制药有限公司 | The method for detecting (1R, 2S) -2- (3,4- difluorophenyl) cyclopropylamine in ticagrelor |
| CN109633063A (en) * | 2018-12-26 | 2019-04-16 | 哈尔滨医科大学 | The detection method of ticagrelor and its active metabolite concentration in a kind of human plasma |
| CN110412188A (en) * | 2018-04-27 | 2019-11-05 | 广东东阳光药业有限公司 | A method of the isomer impurities of separation and measurement ticagrelor intermediate |
| WO2020010740A1 (en) * | 2018-07-09 | 2020-01-16 | 深圳翰宇药业股份有限公司 | Detection method for vildagliptin enantiomer |
| CN112557520A (en) * | 2019-09-25 | 2021-03-26 | 北京济美堂医药研究有限公司 | Method for detecting TGR-1-corresponding isomer in TGR-1 |
| CN112666269A (en) * | 2019-10-16 | 2021-04-16 | 北京科莱博医药开发有限责任公司 | Method for detecting isomer in SAR107375 by using high performance liquid chromatography |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101701942A (en) * | 2009-09-03 | 2010-05-05 | 重庆医药工业研究院有限责任公司 | Method for separating and measuring entecavir and optical isomer thereof by liquid chromatography |
| CN103207248A (en) * | 2012-12-21 | 2013-07-17 | 北京万全德众医药生物技术有限公司 | Method of separating optical isomers of ezetimibe intermediate by using HPLC |
| CN103360396A (en) * | 2013-06-27 | 2013-10-23 | 苏州明锐医药科技有限公司 | Method for preparing ticagrelor |
-
2014
- 2014-11-04 CN CN201410614624.2A patent/CN104634887B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101701942A (en) * | 2009-09-03 | 2010-05-05 | 重庆医药工业研究院有限责任公司 | Method for separating and measuring entecavir and optical isomer thereof by liquid chromatography |
| CN103207248A (en) * | 2012-12-21 | 2013-07-17 | 北京万全德众医药生物技术有限公司 | Method of separating optical isomers of ezetimibe intermediate by using HPLC |
| CN103360396A (en) * | 2013-06-27 | 2013-10-23 | 苏州明锐医药科技有限公司 | Method for preparing ticagrelor |
Non-Patent Citations (3)
| Title |
|---|
| YAN LI ET AL.: "Disposition and Metabolism of Ticagrelor, a Novel P2Y Receptor Antagonist, in Mice, Rats, and Marmosets", 《DRUG METABOLISM AND DISPOSITION》 * |
| 胡剀: "高效液相色谱法测定左舒必利原料有关物质及其异构体", 《今日药学》 * |
| 谢安云 等: "高效液相色谱法测定恩替卡韦分散片全反式异构体", 《医药导报》 * |
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| CN106243108A (en) * | 2015-06-03 | 2016-12-21 | 四川海思科制药有限公司 | A kind of highly purified ticagrelor and preparation method thereof |
| CN105301135B (en) * | 2015-11-20 | 2017-08-01 | 扬子江药业集团有限公司 | The method of chiral isomer content in high performance liquid chromatography detection ticagrelor |
| CN105301135A (en) * | 2015-11-20 | 2016-02-03 | 扬子江药业集团有限公司 | Method for detecting chiral isomer content of ticagrelor by high performance liquid chromatography |
| CN106841413B (en) * | 2015-12-04 | 2020-07-28 | 江苏恒瑞医药股份有限公司 | Ticagrelor enantiomer and diastereoisomer separation and detection method |
| CN106841413A (en) * | 2015-12-04 | 2017-06-13 | 江苏恒瑞医药股份有限公司 | A kind of ticagrelor enantiomter, the method for separating and detecting of diastereoisomer |
| CN105510482A (en) * | 2016-01-29 | 2016-04-20 | 成都百裕制药股份有限公司 | Method for detecting content of isomer impurity in raw material for ticagrelor |
| CN105510482B (en) * | 2016-01-29 | 2018-02-02 | 成都百裕制药股份有限公司 | The detection method of isomer impurities content in a kind of ticagrelor raw material |
| CN105699524A (en) * | 2016-01-29 | 2016-06-22 | 成都百裕制药股份有限公司 | Detection method for content of isomer impurities in Ticagrelor |
| CN106645528A (en) * | 2016-11-25 | 2017-05-10 | 成都欣捷高新技术开发股份有限公司 | High performance liquid chromatography detection method of content of chiral isomers of ticagrelor |
| CN109387578A (en) * | 2017-08-11 | 2019-02-26 | 四川海思科制药有限公司 | The method for detecting (1R, 2S) -2- (3,4- difluorophenyl) cyclopropylamine in ticagrelor |
| CN110412188A (en) * | 2018-04-27 | 2019-11-05 | 广东东阳光药业有限公司 | A method of the isomer impurities of separation and measurement ticagrelor intermediate |
| WO2020010740A1 (en) * | 2018-07-09 | 2020-01-16 | 深圳翰宇药业股份有限公司 | Detection method for vildagliptin enantiomer |
| CN109633063A (en) * | 2018-12-26 | 2019-04-16 | 哈尔滨医科大学 | The detection method of ticagrelor and its active metabolite concentration in a kind of human plasma |
| CN112557520A (en) * | 2019-09-25 | 2021-03-26 | 北京济美堂医药研究有限公司 | Method for detecting TGR-1-corresponding isomer in TGR-1 |
| CN112666269A (en) * | 2019-10-16 | 2021-04-16 | 北京科莱博医药开发有限责任公司 | Method for detecting isomer in SAR107375 by using high performance liquid chromatography |
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