CN101161642A - Method for decomposing chiral mobile phase additive RP-HPLC of fudosteine enantiomer - Google Patents
Method for decomposing chiral mobile phase additive RP-HPLC of fudosteine enantiomer Download PDFInfo
- Publication number
- CN101161642A CN101161642A CNA2007101330102A CN200710133010A CN101161642A CN 101161642 A CN101161642 A CN 101161642A CN A2007101330102 A CNA2007101330102 A CN A2007101330102A CN 200710133010 A CN200710133010 A CN 200710133010A CN 101161642 A CN101161642 A CN 101161642A
- Authority
- CN
- China
- Prior art keywords
- fudosteine
- enantiomorph
- assaying
- separating
- described method
- 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.)
- Pending
Links
Images
Landscapes
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
The present invention belongs to analytical chemistry field, and relates to separation and determination of Fudosteine and the enantiomer thereof (impurity). The present invention adopts RP-HPLC method, and adds a chiral metal synergist into a chromatogram flow phase system to form a tri-diastereoisomer coordination compound, because the obtained diastereoisomer coordination compound has stable structure with energy difference and capability to carry out three-dimensional selective absorption and repulsion reaction with the fixed phase, the two enantiomers can be separated from each other. The method can separate and determine Fudosteine and the enantiomer thereof (impurity), thereby making the quality of both Fudosteine and the agent containing Fudosteine controllable.
Description
Technical field
The invention belongs to the analytical chemistry field, be specifically related to method with high performance liquid chromatography separation determination Fudosteine and preparation enantiomorph (impurity).
Background technology
Fudosteine is a kind of novel expectorant, it belongs to the compound that is had phlegm-dispelling functions by SSP Pharmaceutical Co., Ltd in the class with department's smooth (steine) basic framework of initiative in 1988, the sulfydryl that contains sealing in its structure is metabolised to active free sulfhydryl groups derivative in vivo and plays a role.Its basic role is that goblet cell hyperplasia restraining effect reaches the mucus of respiratory tract, the regulating effect of mucous membrane standard state.It went on the market in Japan first December 17 calendar year 2001, by Mitsubishi's pharmacy and S.S pharmaceutical manufacturing.Formulation is the 200mg tablet, and trade(brand)name is respectively: Cleanal TABLETS (Mitsubishi Pharmaceutical Corp), SPELEAR tablets 200 (S.S Pharmaceutical Co., Ltd).At present domestic existing tablet approval listing, other preparation also will be got permission to produce successively.Fudosteine has multiple pharmacological action to chronic respiratory system diseases, suppresses the airway epithelial cell hyperplasia, can make trehalose in the phlegm/sialic ratio normalizing; improve the viscosity and the elasticity of phlegm; recover cilium and carry the state of air flue juice, promote serous secretion, and anti-inflammatory action is arranged.It is a present unique expectorant with multiple action mechanism.Fudosteine is applicable to that treatment bronchial asthma, chronic bronchitis, bronchiectasis, pulmonary tuberculosis, pulmonary emphysema, atypia acid-fast bacillus infect eliminating the phlegm of chronic respiratory system diseasess such as disease, diffusivity bronchitis.
The chiral drug enantiomorph often has different pharmacologically actives and toxicity, and process is often also different in vivo.Therefore, chiral drug is applied to clinical mostly with single enantiomer.Except that just the opposite to the deflecting direction of polarized light, other physico-chemical property is identical between the chiral drug enantiomeric compounds, thereby is difficult to separate.Research simply, chiral drug recognition methods fast and accurately becomes the main direction of chiral analysis in recent years.Fudosteine (L-fudosteine, S-(3 hydroxypropyls-L-cysteine) is the derivative of cysteine, i.e. L-(-)-Fudosteine; D-(+)-Fudosteine lifeless matter activity.Contain a chiral carbon atom in its molecule, can generate 2 kinds of enantiomorphs that steric configuration is different in the chemosynthesis, see Fig. 1.Set up Fudosteine Chiral Separation and detection method carry out reliable to it and effective quality control significant.
Fig. 1 L-(-)-Fudosteine and D-(+)-Fudosteine enantiomorph molecular structural formula
Chiral drug mapping structure body separates and detection method mainly contains: 1. chiral stationary phase (CSP) method; 2. post prochirality derivatize (CDR) method; 3. chirality moving phase (CMP) method.1. method is simple and quick, but the CSP post costs an arm and a leg; 2. method needs the high-optical-purity chiral derivatization reagent, and derivative reaction is often more loaded down with trivial details time-consuming; 3. the simple and low price of method process.Split in 3 kinds of methods of enantiomorph at HPLC, chirality moving phase additive method (CMP) has its unique advantage, does not need to derive with chiral reagent, does not also need expensive chiral column, as long as chiral reagent is added in the moving phase, just can separate with common positive or reversed-phase column.Because method is simply effective, has caused widely and paid close attention to.The CDR method have bibliographical information (Wang Ying, Hang Taijun. chirality derivatize-rp-hplc method Fudosteine optical purity [J]. pharmacy progress, 2005,29 (9): 421-425).
The present invention's RP-HPLC method in the chiral metal Synergist S-421 95 adding chromatogram flow phase system, forms ternary diastereomer coordination compound, and produces obviously absorption in the ultraviolet region, makes the Fudosteine of former no uv-absorbing be carried out ultra-violet analysis mensuration, sees Fig. 1-2.Because the diastereomer structure of coordination compound that produces is stable and the difference of energy, and adsorbs and rejection with stationary phase generation stereoselectivity, two enantiomorphs are separated.Can separate simply, fast with exactly and measure Fudosteine and contain the enantiomorph (impurity) of Fudosteine preparation by this method.
Summary of the invention
The object of the present invention is to provide a kind of chirality moving phase additive RP-HPLC method method for splitting of Fudosteine enantiomorph, thereby realize separating and measure Fudosteine and contain the enantiomorph (impurity) of Fudosteine preparation simply, fast with exactly.
RP-HPLC of the present invention separates and measures Fudosteine and contain the method for the enantiomorph (impurity) of Fudosteine preparation, is to be chromatographic column with the bonded silica gel; The chromatogram flow phase system that adds organic phase and water composition with the chiral metal Synergist S-421 95.Here said bonded silica gel chromatographic column comprises C
8, C
18, bonded silica gel post such as cyano group, amino, phenyl; Organic phase comprises acetonitrile, methyl alcohol or tetrahydrofuran (THF) etc.; Water comprises pure water or damping fluid, and organic phase and water volume ratio are 0: 100%～90: 10.Here said chirality cooperates reagent to comprise amino acid and derivative (as L-proline(Pro), L-phenylalanine etc.) and tartrate and derivative thereof etc., and the coordination metal comprises Cu
2+, Zn
2+, Ni
2+, Cd
2+Deng; It is 0.5～2.0 that the chiral metal Synergist S-421 95 cooperates the reagent weight ratio by chirality, preferred 0.8～1.3, optimum 1.3.Here used detector comprises ultraviolet, mass spectrum, differential refraction, electrochemistry or evaporation optical flare detector in the said RP-HPLC method.
Fudosteine and the enantiomorph peak sequence that contains the Fudosteine preparation are in the RP-HPLC color atlas of method of the present invention: D-(+)-enantiomorph is preceding, L-(-)-enantiomorph after, the resolution between the enantiomorph is greater than 1.5.The enantiomorph leading peak should be 0.5～2 with the area ratio of postpeak in the color atlas of record.
RP-HPLC of the present invention separates and measures Fudosteine and contain the method for the enantiomorph (impurity) of Fudosteine preparation, can realize by the following method:
(1) gets Fudosteine or the Fudosteine preparation is an amount of,, make the sample solution that every 1ml contains Fudosteine 0.1～10mg with water or moving phase dissolving (preparation filters in case of necessity).
(2) flow rate of mobile phase is 0.5～2.0ml/min, preferred 0.8ml～1.5ml/min; The ultraviolet detection wavelength is 220～300nm, preferred 230～280nm, more preferably 240～270nm.
(3) sample solution 1～100 μ l that gets (1) injects high performance liquid chromatograph, preferred 10～20 μ l sample introductions test.
Chirality moving phase additive RP-HPLC method of the present invention splits and realizes separating and measure Fudosteine and contain the enantiomorph (impurity) of Fudosteine preparation simply, fast with exactly, makes Fudosteine and contain the Fudosteine quality of the pharmaceutical preparations controlled, sees Fig. 3-7.
Description of drawings
Fig. 1 Fudosteine aqueous solution ultraviolet absorpting spectrum
Fig. 2 Fudosteine chiral metal coordination compound ultraviolet absorpting spectrum
Fig. 3,8 Fudosteine raceme HPLC collection of illustrative plates
Fig. 4,10 Fudosteine detectability HPLC collection of illustrative plates
Fig. 5 Fudosteine contrast solution HPLC collection of illustrative plates
Fig. 6,9 Fudosteine enantiomorphs differentiate and check the HPLC collection of illustrative plates
The HPLC collection of illustrative plates is differentiated and checked to Fig. 7 Fudosteine sheet enantiomorph
Embodiment
Following examples are represented practicality of the present invention, and the present invention is not limited.
Embodiment 1
Instrument and condition 1
Tianjin, island 10Avp high performance liquid chromatograph, octadecylsilane chemically bonded silica are weighting agent, (get L-phenylalanine 1.0g with L-phenylalanine solution, copper sulfate 1.3g adds water 1000ml dissolving) be moving phase, the ultraviolet detection wavelength is 275nm, detection limit 1ug/ml sees Fig. 4.
Implementation step
It is an amount of to get the Fudosteine raceme, adds moving phase solution and makes the solution that contains 5mg among every 1ml.Get 20 μ l and inject liquid chromatograph, peak sequence be D-(+)-enantiomorph preceding, L-(-)-enantiomorph after, the resolution between the enantiomorph is greater than 1.5.Number of theoretical plate calculates by L-(-)-enantiomorph peak should be not less than 1000.The enantiomorph leading peak should be 0.5～2 with the area ratio of postpeak in the color atlas of record.About about 9 minutes of general D-(+)-enantiomorph retention time, about about 12 minutes of L-(-)-enantiomorph retention time is seen Fig. 3.
It is an amount of to get Fudosteine, adds moving phase solution and makes the solution that contains Fudosteine 5mg among every 1ml, as need testing solution; Under the chromatographic condition of embodiment 1, to measure need testing solution 20 μ l and inject liquid chromatograph, the main peak retention time should be consistent with L-(-)-enantiomorph peak retention time of racemization Fudosteine in the need testing solution color atlas, sees Fig. 3,5-6.
It is an amount of to get Fudosteine sheet powder, adds moving phase solution and makes the solution that contains Fudosteine 5mg among every 1ml, as need testing solution.Under the chromatographic condition of embodiment 1, to measure need testing solution 20 μ l and inject liquid chromatograph, the main peak retention time should be consistent with L-(-)-enantiomorph peak retention time of racemization Fudosteine in the need testing solution color atlas, sees Fig. 3,5-7.
It is an amount of to get Fudosteine, and accurate the title decides, and adds moving phase solution and makes the solution that contains Fudosteine 5mg among every 1ml approximately, as need testing solution; Get this solution 1ml, put in the 100ml measuring bottle, be diluted to scale solution in contrast with moving phase.Under the chromatographic condition of embodiment 1, measure contrast solution 20 μ l and inject liquid chromatograph, regulate instrumental sensitivity, make principal constituent peak-to-peak height be the 10%-20% of full range, measure need testing solution 20 μ l again and inject liquid chromatograph, the peak area of D-(+)-enantiomorph must not be greater than 1/2 (0.5%) of contrast solution main peak area in the need testing solution color atlas, see Fig. 3, not 5,6 (, not detecting D-(+)-enantiomorph) because the sample optical purity is good.
It is an amount of to get Fudosteine sheet powder, and accurate the title decides, and adds moving phase solution and makes the solution that contains Fudosteine 5mg among every 1ml approximately, as need testing solution; Get this solution 1ml, put in the 100ml measuring bottle, be diluted to scale solution in contrast with moving phase.Under the chromatographic condition of embodiment 1, measure contrast solution 20 μ l and inject liquid chromatograph, regulate instrumental sensitivity, making the principal constituent peak height is the 10%-20% of full range, measure need testing solution 20 μ l again and inject liquid chromatograph, the peak area of D-(+)-enantiomorph must not be greater than 1/2 (0.5%) of contrast solution main peak area in the need testing solution color atlas.See Fig. 3,7 (, not detecting D-(+)-enantiomorph) because the sample optical purity is good.
Get Fudosteine or Fudosteine sheet powder is an amount of, accurately claim surely, add moving phase solution and make the solution that contains Fudosteine 0.5mg among every 1ml approximately, under the chromatographic condition of embodiment 1, measure 20 μ l and inject liquid chromatograph, the record color atlas; Other gets the Fudosteine reference substance solution and compares with method mensuration, calculates the content of Fudosteine in the trial-product.
Embodiment 7
Instrument and condition 2
Tianjin, island 10Avp high performance liquid chromatograph, octadecylsilane chemically bonded silica are weighting agent, and with methyl alcohol: L-phenylalanine solution (is got L-phenylalanine 1.3g, copper sulfate 1.0g adds water 1000ml dissolving) be moving phase at 10: 90, the ultraviolet detection wavelength is 265nm, detection limit 1 μ g/ml sees Figure 10.
Implementation step
It is an amount of to get the Fudosteine raceme, adds moving phase solution and makes the solution that contains 0.5mg among every 1ml.Get 20 μ l and inject liquid chromatograph, peak sequence be D-(+)-enantiomorph preceding, L-(-)-enantiomorph after, the resolution between the enantiomorph is greater than 1.5.Number of theoretical plate calculates by L-(-)-enantiomorph peak should be not less than 1000.The enantiomorph leading peak should be 0.5～2 with the area ratio of postpeak in the color atlas of record.About about 3 minutes of general D-(+)-enantiomorph retention time, about about 3.7 minutes of L-(-)-enantiomorph retention time is seen Fig. 8.
Embodiment 8
It is an amount of to get Fudosteine, adds moving phase solution and makes the solution that contains Fudosteine 5mg among every 1ml, as need testing solution; Under the chromatographic condition of embodiment 2, to measure need testing solution 20 μ l and inject liquid chromatograph, the main peak retention time should be consistent with L-(-)-enantiomorph peak retention time of racemization Fudosteine in the need testing solution color atlas, sees Fig. 9.
Claims (10)
1. the chirality moving phase additive RP-HPLC method method for splitting of a Fudosteine enantiomorph is characterized in that: be chromatographic column with the bonded silica gel; The chromatogram flow phase system that adds organic phase and water composition with the chiral metal Synergist S-421 95.Sample solution injects high performance liquid chromatograph, and detector is measured.
2. according to right 1 described method of separating and assaying, it is characterized in that: the bonded silica gel chromatographic column can be: C
8, C
18, bonded silica gel posts such as cyano group, amino, phenyl, preferred C
18
3. according to right 1 described method of separating and assaying, it is characterized in that: organic phase can be acetonitrile, methyl alcohol or tetrahydrofuran (THF) etc.; Water can be pure water or damping fluid.
4. according to right 1 described method of separating and assaying, it is characterized in that: the organic phase of chromatogram flow phase system and water volume ratio are 0: 100～90: 10, preferred 0: 100～50: 50, and more preferably 0: 100～10: 90.
5. according to right 1 described method of separating and assaying, it is characterized in that: the chiral metal Synergist S-421 95 cooperates reagent and coordination metal to form by chirality, it is amino acid and derivative (as L-proline(Pro), L-phenylalanine etc.) and tartrate and derivative thereof etc. that chirality cooperates reagent, and the coordination metal has Cu
2+, Zn
2+, Ni
2+, Cd
2+Deng.Preferred chirality cooperates reagent L-phenylalanine and coordination metal Cu
2+
6. according to right 1 described method of separating and assaying, it is characterized in that: the chiral metal Synergist S-421 95 cooperates reagent and coordination metal to form by chirality, and its weight ratio is 0.5～2.0, and preferred 0.8～1.3, optimum 1.3.
7. according to right 1 described method of separating and assaying, it is characterized in that: used detector is that ultraviolet, mass spectrum, differential refraction, electrochemistry or evaporation color break-up are penetrated detector, preferred ultraviolet or mass detector.
8. according to right 1 described method of separating and assaying, it is characterized in that: the color atlas peak sequence be D-(+)-enantiomorph preceding, L-(-)-enantiomorph after, the resolution between the enantiomorph is greater than 1.5.The enantiomorph leading peak should be 0.5～2 with the area ratio of postpeak in the color atlas of record.
9. according to right 7 described method of separating and assaying, it is characterized in that: the chiral metal Synergist S-421 95 adds in the chromatogram flow phase system, form ternary diastereomer coordination compound, and produce obviously absorption, make the Fudosteine of former no uv-absorbing be carried out ultraviolet determination in the ultraviolet region.Because the diastereomer structure of coordination compound that produces is stable and the difference of chemical property, and adsorbs and rejection with stationary phase generation stereoselectivity, enantiomorph is separated.The mensuration wavelength of UV-detector is at 220～300nm, preferred 230～280nm, more preferably 240～270nm.
10. according to right 1 described method of separating and assaying, it is characterized in that: said method comprises following steps:
(1) gets Fudosteine or the Fudosteine preparation is an amount of,, filter in case of necessity, make the sample solution that every 1ml contains Fudosteine 0.1～10mg approximately with water or moving phase dissolving.
(2) flow rate of mobile phase is 0.5～2.0ml/min, and the ultraviolet detection wavelength is 220～300nm.
(3) sample solution 1～100 μ l that gets (1) injects high performance liquid chromatograph, tests.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101330102A CN101161642A (en) | 2007-10-10 | 2007-10-10 | Method for decomposing chiral mobile phase additive RP-HPLC of fudosteine enantiomer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101330102A CN101161642A (en) | 2007-10-10 | 2007-10-10 | Method for decomposing chiral mobile phase additive RP-HPLC of fudosteine enantiomer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101161642A true CN101161642A (en) | 2008-04-16 |
Family
ID=39296631
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101330102A Pending CN101161642A (en) | 2007-10-10 | 2007-10-10 | Method for decomposing chiral mobile phase additive RP-HPLC of fudosteine enantiomer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101161642A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104931603A (en) * | 2015-05-13 | 2015-09-23 | 中国医药集团总公司四川抗菌素工业研究所 | Method for measuring fudosteine related substance by using amino column |
| CN107132297A (en) * | 2017-06-30 | 2017-09-05 | 南京普氟生物检测技术有限公司 | A kind of analyzing detecting method of pramiconazole optical isomer |
| CN107167535A (en) * | 2017-07-20 | 2017-09-15 | 南京普氟生物检测技术有限公司 | A kind of method that reversed phase liquid chromatography detects Raltitrexed enantiomter |
| CN107290453A (en) * | 2017-06-29 | 2017-10-24 | 南京普氟生物检测技术有限公司 | The HPLC analysis methods of palonosetron Hcl synthetic mesophase product |
| CN107328874A (en) * | 2017-06-28 | 2017-11-07 | 南京普氟生物检测技术有限公司 | The resolution reagent and method for separating and detecting of a kind of palonosetron hydrochloride optical isomer |
| CN107402203A (en) * | 2016-05-18 | 2017-11-28 | 北京化工大学 | A kind of colour developing and the method for the quick chiral Recognition tartrate enantiomer of ultraviolet spectra |
| CN110849999A (en) * | 2019-12-05 | 2020-02-28 | 吴海靖 | Liquid chromatography method for separating 8-epiloganin and loganin |
| CN112057418A (en) * | 2020-09-24 | 2020-12-11 | 广州帝奇医药技术有限公司 | Fudosteine oral liquid and preparation method thereof |
| CN112881538A (en) * | 2019-11-29 | 2021-06-01 | 江苏正大丰海制药有限公司 | Detection method for impurities and enantiomers in fudosteine and fudosteine tablets |
-
2007
- 2007-10-10 CN CNA2007101330102A patent/CN101161642A/en active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104931603B (en) * | 2015-05-13 | 2019-06-28 | 中国医药集团总公司四川抗菌素工业研究所 | A method of using the related substance of nh 2 column measurement Fudosteine |
| CN104931603A (en) * | 2015-05-13 | 2015-09-23 | 中国医药集团总公司四川抗菌素工业研究所 | Method for measuring fudosteine related substance by using amino column |
| CN107402203A (en) * | 2016-05-18 | 2017-11-28 | 北京化工大学 | A kind of colour developing and the method for the quick chiral Recognition tartrate enantiomer of ultraviolet spectra |
| CN107402203B (en) * | 2016-05-18 | 2019-11-15 | 北京化工大学 | A method of colour developing and the quick chiral Recognition tartrate enantiomer of ultraviolet spectra |
| CN107328874A (en) * | 2017-06-28 | 2017-11-07 | 南京普氟生物检测技术有限公司 | The resolution reagent and method for separating and detecting of a kind of palonosetron hydrochloride optical isomer |
| CN107290453A (en) * | 2017-06-29 | 2017-10-24 | 南京普氟生物检测技术有限公司 | The HPLC analysis methods of palonosetron Hcl synthetic mesophase product |
| CN107132297B (en) * | 2017-06-30 | 2019-08-13 | 方达医药技术(上海)有限公司 | A kind of analyzing detecting method of pramiconazole optical isomer |
| CN107132297A (en) * | 2017-06-30 | 2017-09-05 | 南京普氟生物检测技术有限公司 | A kind of analyzing detecting method of pramiconazole optical isomer |
| CN107167535A (en) * | 2017-07-20 | 2017-09-15 | 南京普氟生物检测技术有限公司 | A kind of method that reversed phase liquid chromatography detects Raltitrexed enantiomter |
| CN107167535B (en) * | 2017-07-20 | 2020-02-04 | 南京和曦生物科技有限公司 | Method for detecting raltitrexed enantiomer by reversed phase liquid chromatography |
| CN112881538A (en) * | 2019-11-29 | 2021-06-01 | 江苏正大丰海制药有限公司 | Detection method for impurities and enantiomers in fudosteine and fudosteine tablets |
| CN110849999A (en) * | 2019-12-05 | 2020-02-28 | 吴海靖 | Liquid chromatography method for separating 8-epiloganin and loganin |
| CN112057418A (en) * | 2020-09-24 | 2020-12-11 | 广州帝奇医药技术有限公司 | Fudosteine oral liquid and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101161642A (en) | Method for decomposing chiral mobile phase additive RP-HPLC of fudosteine enantiomer | |
| Gao et al. | Preparation and evaluation of magnetic molecularly imprinted polymers for the specific enrichment of phloridzin | |
| Hellinghausen et al. | Effective methodologies for enantiomeric separations of 150 pharmacology and toxicology related 1, 2, and 3 amines with core-shell chiral stationary phases | |
| Wang et al. | Direct enantiomeric resolutions of chiral triazole pesticides by high-performance liquid chromatography | |
| US9822089B2 (en) | R type of resveratrol dimer, preparation process therefor and purpose thereof in lowering blood sugar level | |
| Li et al. | A polymer-based zwitterionic stationary phase for hydrophilic interaction chromatography | |
| An et al. | Enantioseparation of fourteen amino alcohols by nonaqueous capillary electrophoresis using lactobionic acid/d-(+)-xylose–boric acid complexes as chiral selectors | |
| CN106706789B (en) | With the method in relation to substance in high effective liquid chromatography for measuring drotaverine hydrochloride injection | |
| CN102288687A (en) | Method for analysing and detecting impurities in ornithine aspartate | |
| CN106226426A (en) | A kind of high performance liquid chromatography splits the method for canagliflozin five-membered ring impurity enantiomer | |
| CN101401880B (en) | Quality control method for Ditong rhinitis drop and mist | |
| CN1877322B (en) | High-efficiency liquid chromatography method for detecting stachydrine content in motherwort | |
| Ren et al. | Prostate cell membrane chromatography–LC/MS method for screening α 1A-adrenoceptor antagonists from Lotus plumule | |
| Torvinen et al. | Noncovalent complexation of monoamine neurotransmitters and related ammonium ions by tetramethoxy tetraglucosylcalix [4] arene | |
| Baker et al. | Derivatization with acetic anhydride: applications to the analysis of biogenic amines and psychiatric drugs by gas chromatography and mass spectrometry | |
| Liu et al. | A simple and efficient method for the extraction and purification of tuberostemonine from Stemonae Radix using an amide group-based monolithic cartridge | |
| CN105699582B (en) | HPLC detection method of 3-aminopiperidine isomer | |
| CN108490087A (en) | A kind of high performance liquid chromatography measuring content of taurine based on Composition distribution | |
| CN101881755B (en) | Method for detecting esmolol hydrochlorid optical isomer by high efficiency liquid chromatography | |
| Mehvar | Liquid chromatographic analysis of propafenone enantiomers in human plasma | |
| CN105823828B (en) | A kind of detection method of 14 hydroxyl of (carbamoyl) methyl, 2 pyrrolidones chiral isomer | |
| CN110031583B (en) | Liquid chromatography method for separating and measuring N-succinyl tryptophan enantiomer | |
| CN102491926B (en) | Method for preparing and purifying tiopronin disulphide | |
| Kim et al. | Reversed-phase high performance liquid chromatographic separation of the enantiomers of terbutaline by derivatization with 2, 3, 4, 6-tetra-o-acetyl-β-D-glucopyranosyl isothiocyanate | |
| Chamsaz et al. | High-performance liquid chromatographic enantioseparation of drugs containing multiple chiral centers on chiral stationary phases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20080416 |