CN108732280A - A kind of method of his Wei of separation detection hydrochloric acid Dacca and its optical isomer - Google Patents
A kind of method of his Wei of separation detection hydrochloric acid Dacca and its optical isomer Download PDFInfo
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- CN108732280A CN108732280A CN201710251802.3A CN201710251802A CN108732280A CN 108732280 A CN108732280 A CN 108732280A CN 201710251802 A CN201710251802 A CN 201710251802A CN 108732280 A CN108732280 A CN 108732280A
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- 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
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Abstract
Present invention relates particularly to the methods of a kind of his Wei of separation detection hydrochloric acid Dacca and its optical isomer.A method of with his Wei of liquid chromatography for separating and determining hydrochloric acid Dacca and its optical isomer (impurity), it is characterized in that, it uses with cellulose iii (3,5- dimethylphenylcarbamates) be filler chiral chromatographic column, be the mixed solution that sodium hexafluoro phosphate, Potassium Hexafluorophosphate, formic acid, acetic acid, phosphoric acid or phosphate aqueous solution and organic phase are acetonitrile or methanol for mobile phase using water phase.His Wei of hydrochloric acid Dacca and its optical isomer (impurity) can be effectively separated by method for separating and detecting of the present invention, and separating degree reaches 3.0 or more, complete baseline separation, so as to the quality of his Wei of accurate and effective control hydrochloric acid Dacca.Using separation method of the present invention, the time of his Wei of separation detection hydrochloric acid Dacca and its optical isomer, method of the invention had many advantages, such as simple, quick, accurate within 30~80 minutes.
Description
Technical field
The present invention relates to analytical chemistry fields, and in particular to his Wei of liquid chromatography for separating and determining hydrochloric acid Dacca and its light
The method for learning isomers.
Background technology
His Wei (Daclatasvir) of hydrochloric acid Dacca, the entitled N of chemistry, N'- [bis- [the 1H- miaows of [1,1'- biphenyl] -4,4'- diyls
Azoles -5,2- diyls-(2S) -2,1- pyrrolidines diyl [(1S) -1- (1- Methylethyls) -2- oxo -2,1- ethane diyl]]] it is double
Carbamic acid C, C'- dimethyl ester-dihydrochloride, shown in structure such as following formula (1)：
His Wei of hydrochloric acid Dacca is a kind of Hepatitis C Virus (HCV) NS5A inhibitor, is applicable in chronic with the treatment of rope fluorine cloth Wei
HCV genotype 1 or 3 infects.His Wei of hydrochloric acid Dacca contains there are four chiral centre, this claims structure as a pair, there is 1 enantiomerism
Body and 8 diastereoisomer impurity, during detecting hydrochloric acid his Wei of Dacca, his Wei (SSSS) of hydrochloric acid Dacca and its mapping are different
Structure body and diastereoisomer impurity are difficult to be totally separated, detect.
Prior art D1, G.Srinivasu1K etc.Development and Validation of the
Chiral HPLC Method for Daclatasvir in GradientElution Mode onAmylose-Based
Immobilized Chiral Stationary Phase, Chromatographia (2016) 79:1457-1467. disclose
Using 3 optical isomers (RSSR, RRRR, SRRS) of his Wei of liquid chromatography separation detection Dacca, the method uses
CHIRALPAK ID-3 (stationary phase is bonding amylose -3- meta-chlorocarbanilates) chiral chromatographic column, mobile phase are
"Mobile PhaseA:MeOH/DEA (diethylamine) (100/0.1, v/v)；Mobile Phase B:ACN (acetonitrile)/DEA
(100/0.1, v/v) ", gradient elution, and using 315nm as Detection wavelength.
In prior art D2, the HPLC methods of 5 kinds of optical isomers measure in his Wei of the hydrochloric acid such as Guo Feng Dacca, Chinese Medicine
Industrial magazine is published, [J] .2016,47 (10):130.4-1307. is disclosed using hplc simultaneous determination hydrochloric acid
His Wei of Dacca and its 5 optical isomers, 5 optical isomers are respectively RSSS, SSRS, RSSR, SRRS, RRRR.Institute
The method of stating uses Chiralpak IC (stationary phase is plain-three (the 3,5- dichlorophenyls carbamate) of binding fibers) chromatography
Column, with methyl tertiary butyl ether (containing 0.1% diethylamine):Methanol (88:12) it is mobile phase, Detection wavelength 305nm.
In prior art described above, the method for his Wei of disclosed separation determination hydrochloric acid Dacca and its optical isomer
It is all made of positive chiral chromatographic column, and can only at most detect his Wei of hydrochloric acid Dacca and its 5 isomers.
Inventor once attempts to use IC, 4.6mm × 250mm, 5 μm of positive chiral chromatographic columns of CHIRALPAK；CHIRALPAK
OD-RH, 4.6mm × 250mm, 5 μm of reverse phase chiral chromatographic columns；5 μ Cellulose-2250 × 4.6mm of phenomenex Lux are anti-
Phase chiral chromatographic column；5 μ Cellulose-3250 × 4.6mm reverse phase chiral chromatographic columns of phenomenex Lux；CHIRALPAK
OJ-RH, 4.6mm × 150mm, 5 μm of reverse phase chiral chromatographic columns etc. are analysis chromatographic column；Using identical or different mobile phase to for examination
Product carry out analysis detection, as a result show separating effect of the above-mentioned chromatographic column to his Wei of the hydrochloric acid Dacca in test sample and its isomers
It is poor, or have impurity interference or peak type poor, adjusting mobile phase ratio cannot also improve well；And phenomenex Lux 5
μ Cellulose-1 (stationary phase is cellulose iii (3,5- dimethylphenylcarbamate)) 250 × 4.6mm, 5 μm of reverse phase hands
The separating effect of property chromatographic column is preferable.
Invention content
The purpose of the present invention is to provide a kind of his Weis of simple and effective high efficiency liquid chromatography for separating and determining hydrochloric acid Dacca
And its method of optical isomer impurity, to realize efficiently separating and surveying for his Wei of hydrochloric acid Dacca and its 9 isomer impurities
It is fixed.
The present invention provides a kind of method with his Wei of liquid chromatography for separating and determining hydrochloric acid Dacca and its isomers (impurity),
It uses with the chiral chromatographic column that cellulose iii (3,5- dimethylphenylcarbamate) is filler, using water phase as hexafluorophosphoric acid
Sodium, Potassium Hexafluorophosphate, formic acid, acetic acid, phosphoric acid or phosphate aqueous solution and organic phase are that the mixed solution of acetonitrile or methanol is stream
Dynamic phase.
In some embodiments, the volume ratio of the water phase of the mobile phase and organic phase is 55:45~65：35.
In some embodiments, the mobile phase is the mixed solution of hexafluorophosphoric acid aqueous solutions of potassium and acetonitrile.
In some embodiments, the mobile phase is a concentration of 10~100mmol/L of hexafluorophosphoric acid aqueous solutions of potassium, and pH is
2.0~2.3.
In some embodiments, it is the stream that retarder thinner, the retarder thinner are used in the method detection process
The mixed solution of dynamic phase or acetonitrile and water.
In some embodiments, the retarder thinner is the mixed solution of acetonitrile and water, wherein the volume of acetonitrile and water
Than being 1:1.
Method of the present invention can be realized according to the following steps：
1) take his Wei sample of hydrochloric acid Dacca and isomer impurities storing solution appropriate, with a certain amount of diluent sample dissolution,
As test sample mark-on solution；
2) instrument parameter is set：The flow velocity of mobile phase, Detection wavelength, chromatographic column column oven temperature；
3) it takes the solution of a certain amount of step 1) as detection sample, injects high performance liquid chromatograph, complete separation determination and reach
Catarrh Wei and its isomers.
In some embodiments, above-mentioned steps 1) described in diluent in per his Wei sample of the hydrochloric Dacca of 1ml diluents
0.5mg。
Above-mentioned steps 2) flow velocity of the mobile phase is 0.5ml/min~1.1ml/min, in some embodiments, flowing
The flow velocity of phase is 1.0ml/min；The Detection wavelength is 304nm, and in some embodiments, the chromatographic column post case temperature is 20
DEG C~40 DEG C, in some embodiments, the chromatographic column post case temperature is 30~35 DEG C.
Above-mentioned steps 3) the sample solution sample size is the 0.1 μ L of μ L~20, in some embodiments, the sample solution
Sample size is 5 μ L.
In some embodiments, described his Wei of high efficiency liquid chromatography for separating and determining hydrochloric acid Dacca and its optical siomerism
The method of body is characterized in：
Chromatographic column：Phenomenex Lux 5u Cellulose-1250 × 4.6mm chiral chromatographic columns；
Mobile phase：Potassium Hexafluorophosphate and acetonitrile mixed solution, wherein Potassium Hexafluorophosphate are the water that 100mmol/L, pH are 2.0
Solution, the mixed volume ratio with acetonitrile are 65:35；
Detector：UV detector, Detection wavelength 304nm；
Diluent：Acetonitrile-water (1:1)；
Flow velocity：1.0mL/min；
Column temperature：30℃.
In some embodiments, described his Wei of high efficiency liquid chromatography for separating and determining hydrochloric acid Dacca and its optical siomerism
The method of body is characterized in：
Chromatographic column：Phenomenex Lux 5u Cellulose-1250 × 4.6mm chiral chromatographic columns；
Mobile phase：Potassium Hexafluorophosphate and acetonitrile mixed solution, wherein Potassium Hexafluorophosphate are the water that 100mmol/L, pH are 2.0
Solution, the mixed volume ratio with acetonitrile are 65：35；
Detector：UV detector, Detection wavelength 304nm；
Diluent：Acetonitrile-water (1:1)；
Flow velocity：1.0mL/min；
Column temperature：35℃.
His Wei of hydrochloric acid Dacca and its 9 isomer impurities can be effectively separated by detection method of the present invention,
The separating degree of his Wei of hydrochloric acid Dacca isomer impurities adjacent thereto reaches 3.0 or more, also reachable between other Isomers impurity
To baseline separation, so as to effectively control the quality of his Wei of hydrochloric acid Dacca.Using separation method of the present invention, separation inspection
The time of his Wei of hydrochloric acid Dacca and its optical isomer is surveyed within 30~80 minutes.The method of the present invention can it is simple, quick,
Accurately separation detection goes out his Wei of hydrochloric acid Dacca and its isomer impurities, the quality control in can be used for producing.
Term defines
Invention is intended to cover all replacement, modification and equivalent technical solutions, they are included in claim such as and define
The scope of the invention in.Those skilled in the art will appreciate that many and similar or equivalent method described herein and material energy
It is enough in the practice present invention.The present invention is not limited to method described herein and material.Combined document, patent and similar
One or more of material are different from the application or (term, term defined in including but not limited to are answered in the case of contradicting
With, described technology etc.), it is subject to the application.
It will further be appreciated that certain features of the present invention, are clearly visible, are carried out in multiple independent embodiments
Description, but can also in combination be provided in single embodiment.Conversely, the various features of the present invention, for brevity,
It is described, but can also be provided individually or with any suitable sub-portfolio in single embodiment.
Unless otherwise stated, all scientific and technical terminologies used in the present invention have with those skilled in the art of the invention's
It is generally understood identical meaning.All patents of the present invention and public publication are integrally incorporated this hair by reference
It is bright.
In content below or hereafter, wordings such as " about " or " about " whether or not using are all to be disclosed that
Number is approximation.Numerical value of each number be possible to will appear 1%, 2%, 5%, 7%, 8%, 10%, 15% or
The differences such as 20%.Whenever disclosing a number with N values, it is any have N+/- 1%, N+/- 2%, N+/- 3%, N+/-
The digital Hui Bei Ming Indeed of 5%, N+/- 7%, N+/- 8%, N+/- 10%, N+/- 15%or values of N+/- 20% it is open, wherein
" +/- " refers to adding deduct.
Mmol refers to mM, and mg refers to milligram, and μ L refer to microlitre, and mL refers to milliliter, and L refers to liter, and min or Minutes refer to minute, mAU
Refer in Agilent high performance liquid chromatograph systems and multiply 1000 as signal unit using A, mm refers to millimeter, and nm refers to nanometer, and DEG C finger is Celsius
Degree.
Description of the drawings
Fig. 1 is the high-efficient liquid phase chromatogram of the separation detection of comparative example；
Fig. 2 is the high-efficient liquid phase chromatogram of 1 blank solvent of embodiment；
Fig. 3 is the high-efficient liquid phase chromatogram of 1 separation detection of embodiment；
Fig. 4 is the high-efficient liquid phase chromatogram of 2 separation detection of embodiment；
Fig. 5 is the high-efficient liquid phase chromatogram of 3 separation detection of embodiment.
Specific implementation mode
For a further understanding of the present invention, the following describes the present invention in detail with reference to examples.
Comparative example 1
Using method described in prior art D2, his Wei of separation detection hydrochloric acid Dacca and its 9 optical isomers, knot are attempted
Fruit find his Wei of hydrochloric acid Dacca and Isomers it is peak-to-peak separating degree it is poor, and there are isomer impurities to wrap up mutually, cannot achieve
Baseline separation, as shown in Figure 1.
Embodiment 1
Testing conditions：
Instrument：Agilent high performance liquid chromatographs, Agilent DAD UV detector, Detection wavelength：304nm；
Chromatographic column：Phenomenex Lux 5u Cellulose-1250 × 4.6mm chiral chromatographic columns；
Diluent：Acetonitrile-water (1:1)；
Mobile phase：Potassium Hexafluorophosphate and acetonitrile mixed solution, wherein Potassium Hexafluorophosphate are the water that 100mmol/L, pH are 2.0
Solution, the mixed proportion with acetonitrile are 65：35；
Flow velocity：1.0mL/min；
Column temperature：35℃；
Sample size：5μL；
Run time：70min
Detecting step：
It takes his Wei Isomers impurity about 5mg of hydrochloric acid Dacca, in the weighed volumetric flask to 5mL, is dissolved and be diluted to methanol
Scale obtains isomer impurities storing solution.
It takes hydrochloric acid Dacca his Wei sample about 25mg, in the accurately weighed volumetric flask to 50mL, 1mL isomer impurities deposits is added
Liquid, then scale is dissolved and is diluted to diluent, it shakes up, as test sample mark-on solution.
Blank solution is diluent.
Blank solution and test sample mark-on solution are taken respectively, are detected analysis by above-mentioned condition, are recorded chromatogram, as a result
See Fig. 2, Fig. 3.17.17 minutes chromatographic peaks of retention time are the chromatographic peak of his Wei (SSSS) of hydrochloric acid Dacca in Fig. 3；24.19 points
The chromatographic peak of clock be his Wei of hydrochloric acid Dacca enantiomter impurity (RRRR), 21.07,27.38,31.79,36.31,39.71,
44.77, be respectively within 51.80,57.41 minutes diastereoisomer impurity SSRR, SSRS of his Wei of hydrochloric acid Dacca, SSSR, RRRS,
RSRR,SRRS,RSRS,RSSR.The separating degree of his Wei of hydrochloric acid Dacca and adjacent isomer impurities is 3.0.
Embodiment 2
Testing conditions：
Instrument：Agilent high performance liquid chromatographs, Agilent DAD UV detector, Detection wavelength：304nm；
Chromatographic column：Phenomenex Lux 5u Cellulose-1250 × 4.6mm chiral chromatographic columns；
Diluent：Acetonitrile-water (1:1)；
Mobile phase：Potassium Hexafluorophosphate and acetonitrile mixed solution, wherein Potassium Hexafluorophosphate are the water that 100mmol/L, pH are 2.0
Solution, the mixed proportion with acetonitrile are 65：35；
Flow velocity：1.0mL/min；
Column temperature：35℃；
Sample size：5μL；
Detecting step：
Hydrochloric acid Dacca his Wei sample about 25mg is taken, it is accurately weighed to 50mL brown measuring bottles, it is dissolved and is diluted to diluent
Scale shakes up, as test solution.
Test solution is taken, analysis is detected by above-mentioned condition, records chromatogram, as a result see Fig. 4.
Fig. 4 proves that the purity of his Wei of hydrochloric acid Dacca reaches bulk pharmaceutical chemicals requirement, and this law can be used for the light of his Wei of hydrochloric acid Dacca
Learn isomer impurities control monitoring.
Embodiment 3
Testing conditions：
Instrument：Agilent high performance liquid chromatographs, Agilent DAD UV detector, Detection wavelength：304nm；
Chromatographic column：Phenomenex Lux 5u Cellulose-1 250 × 4.6mm chiral chromatographic columns；
Diluent：Acetonitrile-water (1:1)；
Mobile phase：Potassium Hexafluorophosphate and acetonitrile mixed solution, wherein Potassium Hexafluorophosphate are the water that 100mmol/L, pH are 2.0
Solution, the mixed proportion with acetonitrile are 65：35；
Flow velocity：1.0mL/min；
Column temperature：30℃；
Sample size：5μL；
Detecting step：
It takes his Wei Isomers impurity about 5mg of hydrochloric acid Dacca, in the weighed volumetric flask to 5mL, is dissolved and be diluted to methanol
Scale obtains isomer impurities storing solution.
It takes hydrochloric acid Dacca his Wei sample about 25mg, in the accurately weighed volumetric flask to 50mL, 1mL isomer impurities deposits is added
Liquid, then scale is dissolved and is diluted to diluent, it shakes up, as test sample mark-on solution.
Test sample mark-on solution is taken, analysis is detected by above-mentioned condition, records chromatogram, as a result see Fig. 5.
Fig. 5 proves that, when column temperature is 30 degree in the chromatographic condition for changing the analysis method, when other conditions are constant, hydrochloric acid reaches
Catarrh Wei and its 9 isomers can also reach baseline separation, the wherein separating degree at his Wei of hydrochloric acid Dacca isomers peak adjacent thereto
It is 3.1.
The embodiment of the invention discloses the methods of a kind of his Wei of separation detection hydrochloric acid Dacca and its optical isomer.This field
Technical staff can use for reference present disclosure, be suitably modified technological parameter realization.In particular, it should be pointed out that all similar replacements
Apparent to those skilled in the art with changing, they are considered as being included in the present invention.The method of the present invention
Be described by preferred embodiment, related personnel obviously can not depart from the content of present invention, in spirit and scope it is right
Method described herein is modified or suitably changes and combines, to realize and apply the technology of the present invention.
Claims (10)
1. a kind of method with his Wei of liquid chromatography for separating and determining hydrochloric acid Dacca and its isomers, which is characterized in that use with
Cellulose iii (3,5- dimethylphenylcarbamate) is the chiral chromatographic column of filler, using water phase as sodium hexafluoro phosphate, hexafluoro
Potassium phosphate, formic acid, acetic acid, phosphoric acid or phosphate aqueous solution and organic phase are that the mixed solution of acetonitrile or methanol is mobile phase.
2. according to the method described in claim 1, the water phase of the mobile phase and the volume ratio of organic phase are 55：45~65：35.
3. according to any methods of claim 1-2, which is characterized in that the mobile phase be hexafluorophosphoric acid aqueous solutions of potassium with
The mixed solution of acetonitrile.
4. according to the method described in claim 3, it is characterized in that, a concentration of the 10 of the hexafluorophosphoric acid aqueous solutions of potassium~
100mmol/L, pH are 2.0~2.3.
5. according to the method described in claim 1, it is characterized in that, using retarder thinner, the retarder thinner in detection process
For the mobile phase or the mixed solution of acetonitrile and water.
6. according to the method described in claim 5, which is characterized in that the retarder thinner is the mixed solution of acetonitrile and water,
In, the volume ratio of acetonitrile and water is 1:1.
7. according to the method described in claim 1, it is characterized in that, comprising the steps of：
1) take his Wei sample of hydrochloric acid Dacca and isomer impurities storing solution appropriate, with a certain amount of diluent sample dissolution, as
Test sample mark-on solution；
2) instrument parameter is set：The flow velocity of mobile phase, Detection wavelength, chromatographic column column oven temperature；
3) take the solution of a certain amount of step 1) as detection sample, inject high performance liquid chromatograph, complete separation determination Dacca he
Wei and its isomers.
8. the method according to the description of claim 7 is characterized in that the flow velocity of the mobile phase is 0.5ml/min~1.1ml/
Min or the flow velocity of mobile phase are 1.0mL/min；The Detection wavelength is 304nm；The chromatographic column post case temperature is 20 DEG C
~40 DEG C or 30 DEG C~35 DEG C.
9. according to the method described in claim 7, it is characterized in that：
Chromatographic column：Phenomenex Lux 5u Cellulose-1 250 × 4.6mm chiral chromatographic columns；
Mobile phase：Potassium Hexafluorophosphate and acetonitrile mixed solution, wherein Potassium Hexafluorophosphate be 100mmol/L, pH be 2.0 it is water-soluble
Liquid, the mixed volume ratio with acetonitrile are 65:35；
Detector：UV detector, Detection wavelength 304nm；
Diluent：Acetonitrile-water (1:1)；
Flow velocity：1.0mL/min；
Column temperature：30℃.
10. according to the method described in claim 7, it is characterized in that：
Chromatographic column：Phenomenex Lux 5u Cellulose-1 250 × 4.6mm chiral chromatographic columns；
Mobile phase：Potassium Hexafluorophosphate and acetonitrile mixed solution, wherein Potassium Hexafluorophosphate be 100mmol/L, pH be 2.0 it is water-soluble
Liquid, the mixed volume ratio with acetonitrile are 65：35；
Detector：UV detector, Detection wavelength 304nm；
Diluent：Acetonitrile-water (1:1)；
Flow velocity：1.0mL/min；
Column temperature：35℃.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110672753A (en) * | 2019-11-04 | 2020-01-10 | 青海省农林科学院 | Method for splitting and detecting fluorochloridone isomer |
| CN111505161A (en) * | 2020-05-11 | 2020-08-07 | 成都市科隆化学品有限公司 | Method for detecting enantiomer of protected amino acid |
| CN112285229A (en) * | 2020-10-19 | 2021-01-29 | 华中科技大学同济医学院附属同济医院 | Quantitative detection method for dalatavir in beagle plasma |
| CN113125626A (en) * | 2021-04-09 | 2021-07-16 | 健民药业集团股份有限公司 | HPLC method for detecting dextroisomer from levetiracetam oral liquid |
| CN115356413A (en) * | 2022-08-17 | 2022-11-18 | 博诺康源(北京)药业科技有限公司 | Method for detecting scopolamine hydrobromide related substances |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103848818A (en) * | 2012-11-29 | 2014-06-11 | 广东东阳光药业有限公司 | Parallel ring compound serving as hepatitis C inhibitor, drug composition and applications of parallel ring compound and drug composition in drugs |
| CN104994858A (en) * | 2012-11-02 | 2015-10-21 | 药品循环公司 | TEC family kinase inhibitor adjuvant therapy |
| CN105263941A (en) * | 2013-03-22 | 2016-01-20 | 亚历山大·瓦西里耶维奇·伊瓦切恩科 | Alkyl 2-{[(2r,3s,5r)-5-(4-amino-2-oxo-2n-pyrimidin-1-yl)-3-hydroxy- tetrahydro-furan-2-yl-methoxy]-phenoxy-phosphoryl-amino}-propionates, nucleoside inhibitors of hcv ns5b rna-polymerase, and methods for producing and use thereof |
| WO2016169573A1 (en) * | 2015-04-20 | 2016-10-27 | Elsebai Mahmoud Fahmi | Sesquiterpene lactones as potent and broad spectrum antiviral compounds against all genotypes of hepatitis c virus (hcv) |
-
2017
- 2017-04-18 CN CN201710251802.3A patent/CN108732280B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104994858A (en) * | 2012-11-02 | 2015-10-21 | 药品循环公司 | TEC family kinase inhibitor adjuvant therapy |
| CN103848818A (en) * | 2012-11-29 | 2014-06-11 | 广东东阳光药业有限公司 | Parallel ring compound serving as hepatitis C inhibitor, drug composition and applications of parallel ring compound and drug composition in drugs |
| CN105263941A (en) * | 2013-03-22 | 2016-01-20 | 亚历山大·瓦西里耶维奇·伊瓦切恩科 | Alkyl 2-{[(2r,3s,5r)-5-(4-amino-2-oxo-2n-pyrimidin-1-yl)-3-hydroxy- tetrahydro-furan-2-yl-methoxy]-phenoxy-phosphoryl-amino}-propionates, nucleoside inhibitors of hcv ns5b rna-polymerase, and methods for producing and use thereof |
| WO2016169573A1 (en) * | 2015-04-20 | 2016-10-27 | Elsebai Mahmoud Fahmi | Sesquiterpene lactones as potent and broad spectrum antiviral compounds against all genotypes of hepatitis c virus (hcv) |
Non-Patent Citations (2)
| Title |
|---|
| G. SRINIVASU 等: "Development and Validation of the Chiral HPLC Method for Daclatasvir in Gradient Elution Mode on Amylose‑Based Immobilized Chiral Stationary Phase", 《CHROMATOGRAPHIA》 * |
| 郭凤 等: "盐酸达卡他韦中5种光学异构体的HPLC法测定", 《中国医药工业杂志》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110672753A (en) * | 2019-11-04 | 2020-01-10 | 青海省农林科学院 | Method for splitting and detecting fluorochloridone isomer |
| CN110672753B (en) * | 2019-11-04 | 2022-05-20 | 青海省农林科学院 | Method for splitting and detecting fluorochloridone isomer |
| CN111505161A (en) * | 2020-05-11 | 2020-08-07 | 成都市科隆化学品有限公司 | Method for detecting enantiomer of protected amino acid |
| CN112285229A (en) * | 2020-10-19 | 2021-01-29 | 华中科技大学同济医学院附属同济医院 | Quantitative detection method for dalatavir in beagle plasma |
| CN113125626A (en) * | 2021-04-09 | 2021-07-16 | 健民药业集团股份有限公司 | HPLC method for detecting dextroisomer from levetiracetam oral liquid |
| CN115356413A (en) * | 2022-08-17 | 2022-11-18 | 博诺康源(北京)药业科技有限公司 | Method for detecting scopolamine hydrobromide related substances |
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Address after: 523808 No.1, Gongye North Road, Songshanhu Park, Dongguan City, Guangdong Province Patentee after: Guangdong Dongyangguang Pharmaceutical Co.,Ltd. Address before: 523808 No. 1 Industrial North Road, Songshan Industrial Park, Songshan, Guangdong, Dongguan, Hubei Patentee before: SUNSHINE LAKE PHARMA Co.,Ltd. |