CN107167530A - A kind of analysis method for determining butanedioic acid Solifenacin neutral body isomers and intermediate - Google Patents
A kind of analysis method for determining butanedioic acid Solifenacin neutral body isomers and intermediate Download PDFInfo
- Publication number
- CN107167530A CN107167530A CN201710332308.XA CN201710332308A CN107167530A CN 107167530 A CN107167530 A CN 107167530A CN 201710332308 A CN201710332308 A CN 201710332308A CN 107167530 A CN107167530 A CN 107167530A
- Authority
- CN
- China
- Prior art keywords
- butanedioic acid
- impurity
- acid solifenacin
- analysis method
- solifenacin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
The present invention is the analysis method of a kind of use high effective liquid chromatography for measuring butanedioic acid Solifenacin neutral body isomers and intermediate.It is characterized in that:Using high performance liquid chromatography, isocratic elution is carried out on amylose three (3,5 xylyl carbamate) bonded silica gel chiral chromatographic column;Mobile phase is n-hexane absolute ethyl alcohol isopropanol diethylamine solution (65:15:20:0.1) (volume ratio);Sample is using flowing phased soln.This method can determine the intermediate of the enantiomter of butanedioic acid Solifenacin, diastereoisomer and two enantiomter each other simultaneously, and more structurally sound guarantee is provided for the synthesis route research and quality control of butanedioic acid Solifenacin.
Description
Technical field
The present invention relates to a kind of analysis method for determining butanedioic acid Solifenacin neutral body isomers and intermediate, it is particularly
With high performance liquid chromatography to the enantiomter each other of the enantiomter of butanedioic acid Solifenacin, diastereoisomer and two
The intermediate method that is separated and quantitative determined.
Background technology
Entitled (3R) -1- azabicyclos [2,2,2] octane -3- bases (the 1S) -1- phenyl -3,4- of butanedioic acid Solifenacin chemistry
Dihydro-isoquinoline -2- (1H)-formic acid esters succinate, is high selectivity bladder m receptor antagonistic, and its agent structure is Suo Li
That is new.
There are 2 chiral centres in butanedioic acid Solifenacin structure, there are 3 kinds of optical isomers;Contain 1 in intermediate structure
, there are 2 kinds of optical isomers in individual chiral centre.According to《Technological guidance's principle of chemicals impurity research》It is required that, it is three-dimensional different
The impurity that structure body should be used as target product is controlled.In addition, the different optical isomer of butanedioic acid Solifenacin has to m receptor
There are different selectivity and affinity, therefore consider to be controlled 3 stereoisomers and 2 intermediates of Solifenacin.
So far, pharmacopoeia of each country does not include butanedioic acid Solifenacin stereoisomer, the detection method of intermediate.Through inspection
The butanedioic acid Solifenacin being related in rope, document and patent does not include it about the separation method of material and stereoisomer
The detection of 2 intermediate compositions of 3 stereoisomers and each other enantiomter.Therefore, set up one kind and utilize efficient liquid phase
Chromatogram accurately quickly determines butanedioic acid Solifenacin neutral body isomers and the short-cut method of intermediate is significant.
The content of the invention
It is an object of the invention to provide a kind of efficient liquid for determining butanedioic acid Solifenacin neutral body isomers and intermediate
Analysis of hplc method, makes main peak and stereoisomer peak, intermediate peak energy enough efficiently separate, is the conjunction of butanedioic acid Solifenacin
More structurally sound foundation is provided into technical study and quality control.
To achieve the above object, the technical scheme is that:
A kind of analysis method for determining butanedioic acid Solifenacin stereoisomer and intermediate, using high performance liquid chromatography
Method, with mobile phase sample dissolution, with amylose-three (3,5- xylyl carbamate) bonded silica gel chiral chromatographic column,
Carry out isocratic elution.
The butanedioic acid Solifenacin (A), and its stereoisomer and intermediate are impurity B, impurity C, impurity D, impurity
E, impurity F (being shown in Table 1).
The butanedioic acid Solifenacin of table 1 and its stereoisomer, the chemical structural formula of intermediate
In methods described, with mobile phase sample dissolution, analytical solution is made.
In methods described, chromatographic column is preferably amylose-three (3,5- xylyl carbamate) bonded silica gel hand
Property chromatographic column, model CHIRALPAK IA, 4.6mm × 250mm, 5 μm.
It is described to flow phase composition for n-hexane of the total volume 50%~80%, absolute ethyl alcohol of the total volume 10%~
25%, isopropanol of the total volume 10%~25%, diethylamine of the total volume 0.05%~0.2%., preferably n-hexane-
Absolute ethyl alcohol-isopropanol-diethylamine solution (65:15:20:0.1) (volume ratio).
In methods described, chromatographic condition is:Detection wavelength is 210~230nm, preferably 220nm;Mobile phase elution rate
For 0.8~1.2mL/min, preferably 1.0mL/min;Chromatogram column temperature is 20~35 DEG C, preferably 30 DEG C;Sample injection volume is
5~20 μ L, preferably 10 μ L.
The beneficial effects of the invention are as follows:The alloisomerism of butanedioic acid Solifenacin can effectively be determined simultaneously within a short period of time
Body and intermediate, the perfect relevant substance detecting method of butanedioic acid Solifenacin, have saved the time, have reduced testing cost, can
For the quality control of butanedioic acid Solifenacin study on the synthesis and production process, make the product of butanedioic acid Solifenacin and its preparation
Quality is guaranteed.
Brief description of the drawings
The high-efficient liquid phase chromatogram of Fig. 1 chromatographic columns 1.
The high-efficient liquid phase chromatogram of Fig. 2 mobile phases condition 1.
The high-efficient liquid phase chromatogram of Fig. 3 mobile phases condition 2.
The high-efficient liquid phase chromatogram of Fig. 4 embodiments 4.
The high-efficient liquid phase chromatogram of Fig. 5 embodiments 5.
In figure:1- butanedioic acid Solifenacins;2- impurity Bs;3- impurity C;4- impurity D;5- impurity Es;6- impurity Fs.
Embodiment
Present disclosure is explained by detailed description below, but does not limit the present invention.
It is below butanedioic acid Solifenacin neutral body isomers of the present invention and the chromatostrip of analysis of medium method
Part screening experiment.
1. the selection of chromatographic column
(1) instrument and chromatographic condition
High performance liquid chromatograph:The highly effective liquid phase chromatographic systems of Agilent 1260 and work station.
Chromatographic column:The chiral chromatographic column of different fillers is selected to be tested respectively, specific filler and model are shown in Table 2.
Mobile phase is n-hexane-isopropanol-diethylamine (80:20:0.1) it is 1.0mL/min, Detection wavelength, to set flow velocity
For 220nm, column temperature is 30 DEG C.
(2) experimental procedure
Take butanedioic acid Solifenacin sample, impurity B, C, D, E, F reference substance appropriate respectively, with flowing phased soln and dilute system
Into in every 1mL containing about butanedioic acid Solifenacin 1mg, the μ g of each impurity about 5 mixed solution, test solution is used as.
(3) assay method and result
Each 10 μ L of above-mentioned solution are taken by (1) chromatographic condition sample introduction, chromatogram is recorded, investigate butanedioic acid Solifenacin with it is each miscellaneous
Separating degree between matter and each impurity.Specific separating resulting is shown in Table 2.
Determine that chromatographic column is amylose-three (3,5- xylyls carbamate) bonded silica gel chromatogram by the experiment
Post (CHIRALPAK IA, 4.6mm × 250mm, 5 μm).
The chromatographic column selection result of table 2
2. the selection of mobile phase
(1) instrument and chromatographic condition
High performance liquid chromatograph:The highly effective liquid phase chromatographic systems of Agilent 1260 and work station.
Chromatographic column:Amylose-three (3,5- xylyls carbamate) bonded silica gel chromatographic column (CHIRALPAK
IA, 4.6mm × 250mm, 5 μm).
Different positive mobile phases is successively selected, setting flow velocity is 1.0mL/min, and Detection wavelength is 220nm, and column temperature is 30
DEG C, tested, the concrete composition of each mobile phase is shown in Table 3.
(2) experimental procedure
Take butanedioic acid Solifenacin sample, impurity B, C, D, E, F reference substance appropriate respectively, with flowing phased soln and dilute system
Into in every 1mL containing about butanedioic acid Solifenacin 1mg, the μ g of each impurity about 5 mixed solution, test solution is used as.
(3) assay method and result
Take each 10 μ L of above-mentioned solution by (1) chromatographic condition distinguish sample introduction, record chromatogram, investigate butanedioic acid Solifenacin with
Separating degree between each impurity and each impurity, the separating resulting of different mobile phases is shown in Table 3.
The mobile phase group of n-hexane-isopropanol-diethylamine and n-hexane-absolute ethyl alcohol-diethylamine is found by the experiment
Into can not meet existing impurity B, C, D, E, F separation.
The selection result of the mobile phase of table 3
Technical scheme is further described below in conjunction with specific embodiment, the embodiment provided is only for illustrating this
Invention, the scope being not intended to be limiting of the invention.
Embodiment 1
The measure of butanedioic acid Solifenacin neutral body isomers and intermediate
(1) instrument and chromatographic condition
High performance liquid chromatograph:The highly effective liquid phase chromatographic systems of Agilent 1260 and work station.
Chromatographic column:Amylose-three (3,5- xylyls carbamate) bonded silica gel chromatographic column (CHIRALPAK
IA, 4.6mm × 250mm, 5 μm).
Mobile phase is n-hexane-absolute ethyl alcohol-isopropanol-diethylamine (80:10:10:0.1) (volume ratio), sets flow velocity
For 1.0mL/min, Detection wavelength is 220nm, and column temperature is 25 DEG C.
(2) experimental procedure
Take butanedioic acid Solifenacin sample, impurity B, C, D, E, F reference substance appropriate respectively, with flowing phased soln and dilute system
Into in every 1mL containing about butanedioic acid Solifenacin 1mg, the μ g of each impurity about 5 mixed solution, test solution is used as.
(3) assay method and result
Take the above-mentioned μ L of solution 10 by (1) chromatographic condition sample introduction, record chromatogram, investigate butanedioic acid Solifenacin and each impurity
And the separating degree between each impurity.As a result show, impurity C and impurity D, impurity E is obviously improved with impurity F separating degree.
Embodiment 2
The measure of butanedioic acid Solifenacin neutral body isomers and intermediate
(1) instrument and chromatographic condition
High performance liquid chromatograph:The highly effective liquid phase chromatographic systems of Agilent 1260 and work station.
Chromatographic column:Amylose-three (3,5- xylyls carbamate) bonded silica gel chromatographic column (CHIRALPAK
IA, 4.6mm × 250mm, 5 μm).
Mobile phase is n-hexane-absolute ethyl alcohol-isopropanol-diethylamine (50:25:25:0.1) (volume ratio), sets flow velocity
For 1.0mL/min, Detection wavelength is 220nm, and column temperature is 25 DEG C.
(2) experimental procedure
Take butanedioic acid Solifenacin sample, impurity B, C, D, E, F reference substance appropriate respectively, with flowing phased soln and dilute system
Into in every 1mL containing about butanedioic acid Solifenacin 1mg, the μ g of each impurity about 5 mixed solution, test solution is used as.
(3) assay method and result
Take the above-mentioned μ L of solution 10 by (1) chromatographic condition sample introduction, record chromatogram, investigate butanedioic acid Solifenacin and each impurity
And the separating degree between each impurity.As a result show, impurity B, C, D are up to baseline separation.
Embodiment 3
The measure of butanedioic acid Solifenacin neutral body isomers and intermediate
(1) instrument and chromatographic condition
High performance liquid chromatograph:The highly effective liquid phase chromatographic systems of Agilent 1260 and work station.
Chromatographic column:Amylose-three (3,5- xylyls carbamate) bonded silica gel chromatographic column (CHIRALPAK
IA, 4.6mm × 250mm, 5 μm).
Mobile phase is n-hexane-absolute ethyl alcohol-isopropanol-diethylamine (65:15:20:0.1) (volume ratio), sets flow velocity
For 1.0mL/min, Detection wavelength is 220nm, and column temperature is 20 DEG C.
(2) experimental procedure
Take butanedioic acid Solifenacin sample, impurity B, C, D, E, F reference substance appropriate respectively, with flowing phased soln and dilute system
Into in every 1mL containing about butanedioic acid Solifenacin 1mg, the μ g of each impurity about 5 mixed solution, test solution is used as.
(3) assay method and result
Take the above-mentioned μ L of solution 10 by (1) chromatographic condition sample introduction, record chromatogram, investigate butanedioic acid Solifenacin and each impurity
And the separating degree between each impurity.As a result show, the separating degree between butanedioic acid Solifenacin and each impurity and each impurity is good,
Each chromatographic peak peak shape is good.Further optimize chromatographic condition such as embodiment 4, on the premise of chromatographic column service life is not influenceed to the greatest extent
Amount shortens analysis time.
Embodiment 4
The measure of butanedioic acid Solifenacin neutral body isomers and intermediate
(1) instrument and chromatographic condition
High performance liquid chromatograph:The highly effective liquid phase chromatographic systems of Agilent 1260 and work station.
Chromatographic column:Amylose-three (3,5- xylyls carbamate) bonded silica gel chromatographic column (CHIRALPAK
IA, 4.6mm × 250mm, 5 μm).
Mobile phase is n-hexane-absolute ethyl alcohol-isopropanol-diethylamine (65:15:20:0.1) (volume ratio), sets flow velocity
For 1.0mL/min, Detection wavelength is 220nm, and column temperature is 30 DEG C.
(2) experimental procedure
Take butanedioic acid Solifenacin sample, impurity B, C, D, E, F reference substance appropriate respectively, with flowing phased soln and dilute system
Into in every 1mL containing about butanedioic acid Solifenacin 1mg, the μ g of each impurity about 5 mixed solution, test solution is used as.
(3) assay method and result
Take the above-mentioned μ L of solution 10 by (1) chromatographic condition sample introduction, record chromatogram, investigate butanedioic acid Solifenacin and each impurity
And the separating degree between each impurity.As a result show, within shorter analysis time, butanedioic acid Solifenacin and each impurity and each miscellaneous
Separating degree between matter is good, and each chromatographic peak peak shape is good (see accompanying drawing 4).
Embodiment 5
The measure of butanedioic acid Solifenacin material three-dimensional isomers and intermediate
(1) instrument and chromatographic condition
High performance liquid chromatograph:The highly effective liquid phase chromatographic systems of Agilent 1260 and work station.
Chromatographic column:Amylose-three (3,5- xylyls carbamate) bonded silica gel chromatographic column (CHIRALPAK
IA, 4.6mm × 250mm, 5 μm).
Mobile phase is n-hexane-absolute ethyl alcohol-isopropanol-diethylamine (65:15:20:0.1) (volume ratio), sets flow velocity
For 1.0mL/min, Detection wavelength is 220nm, and column temperature is 30 DEG C.
(2) experimental procedure
Take butanedioic acid Solifenacin bulk drug appropriate, be made with flowing phased soln and dilution in every 1mL containing about butanedioic acid rope
Li Naxin 1mg solution, is used as need testing solution.
Precision measures need testing solution in right amount, plus mobile phase quantitatively dilutes the solution being made in every 1mL containing about 2 μ g, as
Contrast solution.Take impurity B, C, D reference substance appropriate respectively, be made with flowing phased soln and dilution in every 1mL containing about butanedioic acid rope
The each about 2 μ g of Li Naxin impurity Bs, C, D mixed solution, is used as impurity reference substance solution.
(3) assay method and result
Take the μ L of butanedioic acid Solifenacin impurity reference substance solution 10 to inject liquid chromatograph, record chromatogram, butanedioic acid rope
Li Naxin impurity Bs, impurity C and impurity D flow out successively, and the separating degree between each peak should meet regulation.Need testing solution is taken respectively
Press (1) chromatographic condition sample introduction with each 10 μ L of contrast solution, record chromatogram, in the chromatogram of need testing solution if any with impurity B,
The consistent chromatographic peak of C, D retention time, its peak area cannot be greater than the area (0.2%) of contrast solution main peak, other each impurity
The half (0.1%) of contrast solution main peak area is cannot be greater than, impurity summation must not be crossed (0.5%).
The isomers testing result of 3 batches of butanedioic acid Solifenacins is shown in Table 4, the chromatogram of butanedioic acid Solifenacin raw material (see
Accompanying drawing 5).
The butanedioic acid Solifenacin isomer impurities testing result of table 4
Claims (4)
1. a kind of analysis method for determining butanedioic acid Solifenacin stereoisomer and intermediate, it is characterized in that, using efficient liquid
Phase chromatography, with mobile phase sample dissolution, with the chiral color of amylose-three (3,5- xylyl carbamate) bonded silica gel
Post is composed, isocratic elution is carried out;
The butanedioic acid Solifenacin (A), and its stereoisomer and intermediate be impurity B, it is impurity C, impurity D, impurity E, miscellaneous
Matter F:
It is described to flow phase composition for n-hexane of the total volume 50%~80%, absolute ethyl alcohol of the total volume 10%~25%,
Isopropanol of the total volume 10%~25%, diethylamine of the total volume 0.05%~0.2%.
2. analysis method as claimed in claim 1, it is characterized in that, flowing phase composition be n-hexane-absolute ethyl alcohol-isopropanol-
Diethylamine solution (65:15:20:0.1) (volume ratio).
3. analysis method as claimed in claim 1, it is characterized in that, described chromatographic column for CHIRALPAK IA, 4.6mm ×
250mm, 5 μm.
4. analysis method as claimed in claim 1, it is characterized in that, chromatographic condition includes:Detection wavelength is 220nm;Mobile phase
Elution rate is 1.0mL/min;Chromatogram column temperature is 30 DEG C;Sample injection volume is 10 μ L.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710332308.XA CN107167530B (en) | 2017-05-12 | 2017-05-12 | Analysis method for determining stereoisomer and intermediate in solifenacin succinate |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710332308.XA CN107167530B (en) | 2017-05-12 | 2017-05-12 | Analysis method for determining stereoisomer and intermediate in solifenacin succinate |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107167530A true CN107167530A (en) | 2017-09-15 |
CN107167530B CN107167530B (en) | 2020-02-28 |
Family
ID=59815598
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710332308.XA Active CN107167530B (en) | 2017-05-12 | 2017-05-12 | Analysis method for determining stereoisomer and intermediate in solifenacin succinate |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107167530B (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107907605A (en) * | 2017-11-07 | 2018-04-13 | 中山奕安泰医药科技有限公司 | A kind of detection method of (1S, 3R) solifenacin |
CN107976493A (en) * | 2017-11-07 | 2018-05-01 | 中山奕安泰医药科技有限公司 | The detection method of one kind (S) -1- phenyl -1,2,3,4- tetrahydroisoquinolines |
CN109374808A (en) * | 2018-11-08 | 2019-02-22 | 南京明捷生物医药检测有限公司 | The method for measuring phenyl amines genotoxicity impurity in succinic acid Suo Li sodium new raw material medicine |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110319621A1 (en) * | 2009-03-09 | 2011-12-29 | Megafine Pharma(P) Ltd. | Method for the preparation of solifenacin and intermediate thereof |
CN103353492A (en) * | 2013-06-29 | 2013-10-16 | 北京万全德众医药生物技术有限公司 | Method of separating and measuring solifenacin succinate raw material and preparation thereof by using liquid chromatography |
CN103760286A (en) * | 2014-01-14 | 2014-04-30 | 北京万全德众医药生物技术有限公司 | Method for measuring optical purity of solifenacin succinate intermediate by high-performance liquid chromatography |
CN104133011A (en) * | 2014-07-01 | 2014-11-05 | 北京万全德众医药生物技术有限公司 | Method for separating and analyzing solifenacin succinate intermediate and correlated substances |
-
2017
- 2017-05-12 CN CN201710332308.XA patent/CN107167530B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110319621A1 (en) * | 2009-03-09 | 2011-12-29 | Megafine Pharma(P) Ltd. | Method for the preparation of solifenacin and intermediate thereof |
CN103353492A (en) * | 2013-06-29 | 2013-10-16 | 北京万全德众医药生物技术有限公司 | Method of separating and measuring solifenacin succinate raw material and preparation thereof by using liquid chromatography |
CN103760286A (en) * | 2014-01-14 | 2014-04-30 | 北京万全德众医药生物技术有限公司 | Method for measuring optical purity of solifenacin succinate intermediate by high-performance liquid chromatography |
CN104133011A (en) * | 2014-07-01 | 2014-11-05 | 北京万全德众医药生物技术有限公司 | Method for separating and analyzing solifenacin succinate intermediate and correlated substances |
Non-Patent Citations (2)
Title |
---|
SHASHIKANT B. LANDGE ET AL.: "Development and Validation of New Chromatographic Method for the Determination of Enantiomeric and Diastereomeric Purity of Solifenacin Succinate: An Antimuscarinic Agent", 《CHROMATOGRAPHY RESEARCH INTERNATIONAL》 * |
王东武 等: "手性固定相高效液相色谱法同时测定琥珀酸索利那新原料药中对映异构体和非对映异构体", 《分析测试学报》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107907605A (en) * | 2017-11-07 | 2018-04-13 | 中山奕安泰医药科技有限公司 | A kind of detection method of (1S, 3R) solifenacin |
CN107976493A (en) * | 2017-11-07 | 2018-05-01 | 中山奕安泰医药科技有限公司 | The detection method of one kind (S) -1- phenyl -1,2,3,4- tetrahydroisoquinolines |
CN109374808A (en) * | 2018-11-08 | 2019-02-22 | 南京明捷生物医药检测有限公司 | The method for measuring phenyl amines genotoxicity impurity in succinic acid Suo Li sodium new raw material medicine |
Also Published As
Publication number | Publication date |
---|---|
CN107167530B (en) | 2020-02-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107167530A (en) | A kind of analysis method for determining butanedioic acid Solifenacin neutral body isomers and intermediate | |
CN105004802B (en) | The method and application of separation determination razaxaban and its impurity | |
Zhang et al. | Bioanalytical methods for the determination of antipsychotic drugs | |
CN109406695B (en) | High performance liquid chromatography for simultaneously separating and analyzing paricalcitol and isomer impurities in paricalcitol injection | |
Kumari et al. | Chromatographic techniques: types, principles, and applications | |
CN106908525A (en) | A kind of analysis method for determining SC 69124 intermediate and SC 69124 about material | |
CN101685084B (en) | Method for detecting methylnaltrexone bromide and impurity thereof by chromatography | |
Tavakoli et al. | Characterization and performance evaluation of functional monomer effect on molecular imprinted polyurethane foam | |
CN108152394A (en) | A kind of method of isomers in separation determination Ezetimibe | |
CN111380993B (en) | Method for analyzing related substances of roxasistat | |
Ampasavate et al. | Transport and metabolism of opioid peptides across BeWo cells, an in vitro model of the placental barrier | |
CN103645259B (en) | Method for simultaneously determining 4-amino-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione and related substances thereof | |
CN109557218A (en) | The chromatogram analysis method of AHU377 and its isomers | |
CN107192766A (en) | A kind of method that Su Woleisheng chiral isomers are determined with HPLC | |
CN105445384B (en) | The method for separating and detecting of 3 chlorobenzene propyl alcohol optical isomers and its application | |
CN103575813A (en) | HPLC analysis method for alvimopan or related compounds of the alvimopan | |
Blahova et al. | Approaches in sample handling before HPLC analysis of complex matrices | |
CN107782800A (en) | The method of high-efficient liquid phase chromatogram technique analysis separation support pyrrole department he and its impurity | |
JP4644948B2 (en) | Lipoprotein analysis method | |
CN103884783B (en) | A kind of analyzing detecting method of ivabradine midbody | |
CN107167542B (en) | A centrifugal device for phosphopeptide enrichment and separation | |
CN111983075A (en) | Method for detecting rasagiline and enantiomer thereof | |
CN104897797A (en) | Method for determining oleanolic acid content and ursolic acid content in perilla frutescens oil through high performance liquid chromatography method | |
CN106153756A (en) | A kind of detect the high performance liquid chromatography of rapamycin in everolimus | |
CN105301122A (en) | Method for determination of contents of oleanolic acid and ursolic acid in kiwi fruit oil through high performance liquid chromatography |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |