CN105954419A - Method for separating and determining levocetirizine hydrochloride and enantiomer thereof through HPLC method - Google Patents
Method for separating and determining levocetirizine hydrochloride and enantiomer thereof through HPLC method Download PDFInfo
- Publication number
- CN105954419A CN105954419A CN201610382247.3A CN201610382247A CN105954419A CN 105954419 A CN105954419 A CN 105954419A CN 201610382247 A CN201610382247 A CN 201610382247A CN 105954419 A CN105954419 A CN 105954419A
- Authority
- CN
- China
- Prior art keywords
- enantiomer
- mobile phase
- levo
- cetirizine hydrochloride
- solution
- 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
-
- 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid 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)
Abstract
The invention belongs to the field of analytical chemistry, and particularly relates to a method for separating and determining levocetirizine hydrochloride and enantiomer thereof through an HPLC method. In the method, an adopted chromatographic column takes silica gel of which the surface is chemically bonded with beta-cyclodextrin as filler, elution is conducted through a mobile phase A and a mobile phase B, and detection is conducted by entering a detector; the mobile phase A is an inorganic salt buffer system, and the mobile phase B is organic solvent. The method is a reversed phase high performance liquid chromatography method, separation and determination of levocetirizine hydrochloride and the enantiomer thereof can be achieved simultaneously, excellent separation performance and durability are achieved, the method is simple, convenient, feasible, good in reproducibility, efficient and rapid, the analysis time is significantly shortened, the tailing factor and theoretical pedal number can both reach very good effects, the content of the enantiomer in levocetirizine hydrochloride can be effectively determined, and specificity is high.
Description
Technical field
The invention belongs to analytical chemistry field, be specifically related to a kind of left west of HPLC method separation determination hydrochloric acid for profit
Piperazine and the method for enantiomer thereof.
Background technology
Levo-cetirizine hydrochloride (Levocetirizine Hydrochloride) listed February calendar year 2001, was the
Three generations's antihistaminic, is that (cetirizine TP-is different for the single optical isomer of second filial generation antihistaminic cetirizine
Structure body), UCB. S.A. (BE) Bruxelles Belgium research and develop, for selectivity histamine H l receptor antagonist, without obvious cholinolytic and anti-
The effect of 5-hydroxy tryptamine, central inhibitory action is less, is mainly used in treating respiratory system, skin and eyes etc.
The anaphylactic disease at place, such as allergic rhinoconjunctivitis, anaphylaxis dermatosis, allergic asthma etc., has work
By rapid-action, the effect lasting and advantage of few side effects by force.
It is extensive that levo-cetirizine hydrochloride is suitable for crowd, can be used for child and trimester of pregnancy and women breast-feeding their children, safely,
Reliably, clinical effectiveness is notable.Levo-cetirizine hydrochloride chemical name R-2-[2-[4-[(4-chlorphenyl) phenyl methyl]-1-
Piperazinyl] ethyoxyl] acetic acid, dihydrochloride, molecular formula is C21H25ClN2O3·2HCl.The left west of hydrochloric acid is for profit
Piperazine structural formula is:
Chemical name and the structural formula of isomer are as follows:
The curative effect clinical research process of the test of the cetirizine enantiomer carried out finds, left-handed
Cetirizine curative effect is better than its raceme cetirizine, and dextrocetirizine does not then have any drug action.
Owing to the two pharmacologically exists bigger difference, therefore pharmaceutical synthesis and production process need west left to hydrochloric acid
Enantiomer impurity content for profit piperazine strictly controls.And the enantiomer containing chiral carbon atom
Analyze, separate difficult point and the emphasis of quality control in always chiral drug synthesis and production process, it is achieved salt
Separating at the synthesis of levo-cetirizine hydrochloride medicine and production process of acid levocetirizine and corresponding isomer thereof
Quality control aspect there is very important social meaning and economic benefit.
For the isomer produced during preparing levo-cetirizine hydrochloride, whether at crude drug or preparation
In be required to strictly control.At present USP records medicine levo-cetirizine hydrochloride, and have isomery
Body detecting method, but levo-cetirizine hydrochloride isomer detection method in USP, appearance time is very late, main
Peak appearance time is 35 minutes, and a sample needle at least needs 60 minutes, and symmetrical factor is very big, theoretical
Pedal number is the highest.Publication date is protein and the cellulose derivative chiral stationarity separated salt of 20041231
Acid levocetirizine enantiomer, Zhang Zhefeng, limit in Acta Pharmaceutica Sinica is protein and cellulose derivative hands
Property fix phase, and this method uses with the silica gel of surface chemistry bonding beta-schardinger dextrin-as filler, specifically adopts
Using ULTRON ES-CD, this chromatographic column has excellent separating property and durability.Application No.
201010595648.X patent of invention disclose a kind of analytical separation levocetirizine and optical isomer thereof
Detection method, the method uses CHIRAL-AGP chiral column, for normal phase chromatography.First
Chromatographic column filler is α1-acid glycoprotein, service life is the longest, it is easy to bad.Secondly this patented method is reported as
Normal phase chromatography, normal phase chromatography taste weight, toxicity is big.There is presently no a kind of silicon using beta-schardinger dextrin-
Glue is filler, and can durable in use, environmental protection, toxicity little, and can also sharp separation levo-cetirizine hydrochloride
And the open method report of enantiomer.
Therefore developing with the silica gel of beta-schardinger dextrin-as filler, durable in use, environmental protection, toxicity is little and can quickly divide
From the analysis method of levo-cetirizine hydrochloride and enantiomer thereof, for pharmaceutical analysis personnel health and product thereof
The quality control of product and degradation pathway research are all the most significant work.
Summary of the invention
In view of this, it is an object of the invention to provide a kind of HPLC method separation determination levo-cetirizine hydrochloride
And the method for enantiomer, the method is reversed phase high-performance liquid chromatography, can realize the left west of hydrochloric acid simultaneously
Replace profit piperazine and the separation of enantiomer thereof and detection, and have excellent separating property and durability, significantly contract
Short analysis time, tailing factor and theoretical pedal number all can reach extraordinary effect.
For achieving the above object, the technical scheme is that
A kind of HPLC (high performance liquid chromatography) method separation determination levo-cetirizine hydrochloride and enantiomer thereof
Method, in described method use chromatographic column be with surface chemistry bonding beta-schardinger dextrin-silica gel as filler,
Use mobile phase A and Mobile phase B to carry out eluting, enter detector and detect；Described mobile phase A
For inorganic salt buffer system, described Mobile phase B is organic solvent.
Described levo-cetirizine hydrochloride structural formula is:
Chemical name and the structural formula of described levo-cetirizine hydrochloride enantiomer are as follows:
When splitting enantiomer with cyclodextrin chiral Bonded Phase, the structure of sample there is is particular/special requirement, one
Being that sample molecule part must can enter cyclodextrin inner chamber, two is the polar group on sample molecule chiral centre
Group and the hydroxyl generation association in cyclodextrin cavity.The compound that the present invention is separated contains phenyl ring, can be with
Cyclodextrin inner chamber occurs to contain complexing, can form hydrogen with the hydroxyl of cyclodextrin accent and build, so hydrochloric acid is left
Cetirizine and enantiomer thereof can preferably be separated on cyclodextrin bonded stationary phase.
Preferred as one, that described chromatographic column selects is ULTRON ES-CD, ULTRON ES-CD:
ES-CD chiral stationary phase is beta-schardinger dextrin-, and ES-CD has excellent separating property and durability.ES-CD
With post to the flowing of anti-phase positive mutually can, be applied to hydrophobic cyclic agent, pesticide and organic compound
Chiral separation.
Further, in described inorganic salt buffer system, the concentration of inorganic salt is 0.04mol/L-0.06mol/L.
Preferred as one, in described inorganic salt buffer system, the concentration of inorganic salt is 0.05mol/L.
Further, described inorganic salt buffer system is the buffer system of Potassium Hexafluorophosphate.
The factor affecting chiral separation is a lot, under the conditions of the fixing phase determined, for the sample determined,
The composition of flowing phase is the key factor that impact separates.Hexafluorophosphoric acid potassium concn is high, mixes easily with acetonitrile
Separating out solid, concentration is low does not reaches ion-pairing agent effect, thus select concentration range for for
0.04mol/L-0.06mol/L。
Further, described inorganic salt buffer system pH value is 2-4.
Selectivity and the usefulness of cyclodextrin bonded phase are had a great impact by pH and the ionic strength of flowing phase,
Adding salt in flowing mutually, form buffer solution, the comparison that affects on reservation and usefulness optionally affects greatly,
Owing to buffer agent captures cyclodextrin cavity with analyte competition, so increasing with the intensity of buffer agent, solute
Retaining and reduce, usefulness increases.Non-dissociable solute is had a great impact by the change of flowing phase pH.
Preferred as one, described inorganic salt buffer system pH value is 3.0.
Further, described mobile phase A and volume ratio 60:40 of Mobile phase B；Described organic solvent includes
Acetonitrile.
In the chiral separation rp mode of cyclodextrin bonded phase, typically can use in flowing mutually is organic molten
Agent has: methanol, ethanol, propanol, acetonitrile, dimethylformamide, dioxane etc., but uses most
It is methanol and acetonitrile.The generally ability at water cyclodextrin inclusion organic molecule is the strongest, along with organic modifiers
Addition, occupy cyclodextrin inner chamber owing to organic modifiers and solute molecule are vied each other, make Binding ability drop
Low, methanol is the displacer that alcohol apoplexy due to endogenous wind is the most weak, and the replacement ability of acetonitrile is stronger than methanol and ethanol.Select not
Same organic solvent, can improve the selectivity of Chiral Separation.
Further, described flow rate of mobile phase is 0.3-0.7ml/min, and described chromatographic column post case temperature is 20-30 DEG C.
The binding constant of cyclodextrin is influenced by temperature very big by solute, and binding constant increases at low temperatures, but
Matter transmission can be deteriorated, and the selectivity of cyclodextrin bonded phase can be made to increase so reducing column temperature, being likely to meeting simultaneously
Make separating degree reduce, but increase column temperature and the separation of the strong solute retained can be made moderate progress, so through overtesting
Checking, chromatographic column post case temperature range is chosen as 20-30 DEG C.
Further, the specification of described chromatographic column is 150 × 6.0mm, 5 μm.
ULTRON ES-CD analytical column to this specification, optimal flow rate of mobile phase scope should be
0.3-0.7ml/min, the peak diffusion that (0.7-2.0ml/min) causes due to matter transmission effects under high flow rate can be led
Cause to reduce post effect and separating degree.
Further, the detection wavelength of described detector is 220-240nm.
Further, described HPLC method separation determination levo-cetirizine hydrochloride and the method for enantiomer thereof,
Specifically include following steps:
1) take the reference substance of levo-cetirizine hydrochloride and enantiomer thereof respectively, dissolve to make with diluent and treat
Test sample product and the reference substance solution of enantiomer thereof, take testing sample levo-cetirizine hydrochloride and right respectively
Reflect the reference substance solution sample introduction of isomer, carry out efficient liquid phase chromatographic analysis, determine levo-cetirizine hydrochloride and
The retention time of its enantiomer；
2) take levo-cetirizine hydrochloride test sample to add diluent and make need testing solution, then take diluent conduct
Blank solution, takes need testing solution and blank solution sample introduction respectively, carries out efficient liquid phase chromatographic analysis, record
Chromatogram, completes the separation determination of levo-cetirizine hydrochloride and enantiomer thereof.
Further, step 1) described diluent is the aqueous dissolution sample of acetonitrile or acetonitrile, institute's acetonitrile
In aqueous solution, the volume ratio of acetonitrile and water is 40:60.
Method of the present invention, preferred as one, specifically can realize in accordance with the following methods:
(1) levo-cetirizine hydrochloride is taken appropriate, with 40% acetonitrile solution (acetonitrile V: water V=40:60)
Sample dissolution, is configured to the sample solution of every 1ml hydrochloric levocetirizine 0.1-0.5mg；
(2) selecting model is the chromatograph of Shimadzu LC-20AT, and chromatographic column model is ULTRON ES-CD
(150 × 6.0mm), the preparation of mobile phase A: weigh Potassium Hexafluorophosphate 9.25g (0.05mol/L hexafluoro phosphorus
Acid potassium) in 1000ml volumetric flask, it is dissolved in water and is diluted to scale, with phosphorus acid for adjusting pH value to 3.0 ± 0.1；
Mobile phase B is acetonitrile；The ratio of mobile phase A and Mobile phase B is 60:40, takes the sample of step (1)
Solution 10 μ l injects in chromatograph of liquid, and arranging flow rate of mobile phase is 0.5ml/min, and detection wavelength is 231nm,
Chromatographic column post case temperature is 25 DEG C, completes levo-cetirizine hydrochloride and the separation of enantiomer thereof and mensuration.
A kind of fixing phase of offer is provided and flowing is replaced in separation and/or the mensuration left west of hydrochloric acid
Application in the chromatography of profit piperazine and enantiomer thereof, described fixing mutually for surface chemistry bonding beta-schardinger dextrin-
Silica gel, described flowing is buffer system and the organic solvent of Potassium Hexafluorophosphate mutually, and described Potassium Hexafluorophosphate is molten
The concentration of liquid is 0.04mol/L-0.06mol/L；The pH value of described hexafluorophosphoric acid potassium solution is 2-4；Described have
Machine solvent is acetonitrile.
The beneficial effects of the present invention is:
1) a kind of HPLC method separation determination levo-cetirizine hydrochloride of the present invention and the method for enantiomer thereof,
Use reversed phase high-performance liquid chromatography that levo-cetirizine hydrochloride and enantiomer thereof are separated and detected,
In 25 minutes, levo-cetirizine hydrochloride and enantiomer thereof can be kept completely separate and detect, significantly contract
Short disengaging time, and have excellent separating property and durability.
2) present invention is with the silica gel of beta-schardinger dextrin-as filler, this filler is durable in use, environmental protection, toxicity are little and
Energy sharp separation levo-cetirizine hydrochloride and the analysis method of enantiomer thereof, be good for for pharmaceutical analysis personnel
The quality control of health and products thereof and degradation pathway research are all the most significant work.
3) present invention solves the separation determination problem of levo-cetirizine hydrochloride and enantiomer thereof, the method
Separating degree is good, and specificity is strong, highly sensitive；And simple to operate, there is simplicity, quick advantage, thus
Ensure that the quality controllable of levo-cetirizine hydrochloride and preparation thereof, and finally determine the safe and effective of product, right
Significant in the quality control of levo-cetirizine hydrochloride.
Accompanying drawing explanation
Fig. 1 is the high-efficient liquid phase chromatogram of blank solvent.
Fig. 2 is the mixed solution high-efficient liquid phase chromatogram of levo-cetirizine hydrochloride and enantiomer thereof.
Detailed description of the invention
Hereinafter with reference to accompanying drawing, the preferred embodiments of the present invention are described in detail.In preferred embodiment not
Indicating the experimental technique of actual conditions, generally according to normal condition, illustrated embodiment is in order to preferably to this
The content of invention illustrates, but is not that present disclosure is only limitted to illustrated embodiment.So being familiar with this
The technical staff in field carries out nonessential improvement and adjustment according to foregoing invention content to embodiment, still belongs to
In protection scope of the present invention.
In following example, instrument and the chromatographic condition of employing are as follows:
High performance liquid chromatograph: Shimadzu LC-20AT
Chromatographic column: ULTRON ES-CD (150 × 6.0mm)
Flowing phase:
Mobile phase A: inorganic salt buffer system buffer salt: weigh Potassium Hexafluorophosphate 9.25g (0.05mol/L six
Fluorophosphoric acid potassium) in 1000ml volumetric flask, it is dissolved in water and is diluted to scale, with phosphorus acid for adjusting pH value extremely
3.0±0.1；
Mobile phase B: acetonitrile
The ratio of mobile phase A and Mobile phase B is 60:40
Detector detection wavelength: 231nm
Flow rate of mobile phase: 0.5ml/min
Chromatographic column post box column temperature: 25 DEG C
Sample size: 10 μ l
Diluent (dissolves reference substance and the solvent of testing sample): 40% acetonitrile (acetonitrile V: water V=40:
60)。
Embodiment 1 separation determination levo-cetirizine hydrochloride and enantiomer thereof
The preparation of enantiomerism liquid solution: take enantiomer reference substance about 25mg respectively, put 100ml measuring bottle
In, add diluent and dissolve and be diluted to scale, shake up, obtain enantiomer stock solution.Precision pipettes
Above-mentioned solution 0.5ml, puts in 100ml measuring bottle, adds diluent and is diluted to scale, shake up, obtains mapping different
Structure bulk concentration is the reference substance liquid of 1.25 μ g/ml.
The preparation of mixed solution: weigh levo-cetirizine hydrochloride about 25mg, puts in 100ml measuring bottle, accurate
Pipette enantiomer stock solution 0.5ml, put in above-mentioned same measuring bottle, add diluent and dissolve and be diluted to carve
Degree, shakes up, to obtain final product.
Taking diluent and mixed solution respectively by above-mentioned chromatographic condition sample introduction, record chromatogram, measurement result is shown in
Table 1.Result is shown in Fig. 1, Fig. 2.
Table 1 test determination result
Conclusion: plain dilution agent not disturbed specimen measures；Main peak and the peak-to-peak separating degree of enantiomer are more than 1.5；
Above-mentioned test proves that levo-cetirizine hydrochloride separates well with enantiomer peak, and specificity is strong.
Comparative example 1
In this comparative example, except the mobile phase A used is different, remaining condition all with embodiment 1 phase
With.
Mobile phase A: water.
Taking mixed solution by above-mentioned chromatographic condition sample introduction, record chromatogram, measurement result is shown in Table 2.
Table 2 test determination result
Conclusion: be only in the separation test that mobile phase A is different identical from other conditions of above-described embodiment, salt
Acid levocetirizine and stage enantiomer separation degree are less than 1.5, and main peak tailing factor is more than 2.0, it is impossible to
Meet levo-cetirizine hydrochloride to be effectively separated with enantiomer.
Comparative example 2
In this comparative example, except the mobile phase A used is different, remaining condition all with embodiment 1 phase
With.
Mobile phase A: inorganic salt buffer system buffer salt: weigh potassium dihydrogen phosphate 6.8g (0.05mol/L phosphoric acid
Potassium dihydrogen) in 1000ml volumetric flask, it is dissolved in water and is diluted to scale, with phosphorus acid for adjusting pH value extremely
3.0±0.1。
Taking mixed solution by above-mentioned chromatographic condition sample introduction, record chromatogram, measurement result is shown in Table 3.
Table 3 test determination result
Conclusion: be only in the separation test that mobile phase A is different identical from other conditions of above-described embodiment, salt
Acid levocetirizine and stage enantiomer separation degree are less than 1.5, and main peak tailing factor is more than 2.0, it is impossible to
Reach the requirement that levo-cetirizine hydrochloride efficiently separates with enantiomer.
Embodiment 2 chromatographic system is basic to detection limit, the quantitative limit of levo-cetirizine hydrochloride and enantiomer
Research
Quantitative limit solution: precision weighs levo-cetirizine hydrochloride with enantiomer according to product, is made into finite concentration
Solution, and stepwise dilution obtains quantitative limit solution, as shown in table 2.
Detection limit solution: precision pipettes quantitative limit solution 7.0ml, puts in 20ml measuring bottle, adds diluent dilution
To scale, shake up, limit solution must be detected, as shown in table 3.
Assay method:
Take above-mentioned quantitative limit solution continuous sample introduction 3 times, detection limit solution continuous sample introduction 2 times, calculate main peak peak
The high ratio (signal to noise ratio) with noise.Record chromatogram, result of the test is shown in Table 4 and table 5.
Table 4 quantitative limit measurement result
Table 5 detection limit measurement result
Conclusion: knowable to upper watch test data, under this chromatographic system, levo-cetirizine hydrochloride and enantiomerism
The detection limit of body, quantitative limit correspond with S/N=3 (10): the requirement of 1.
Finally illustrate, above example only in order to technical scheme to be described and unrestricted, although
With reference to preferred embodiment, the present invention is described in detail, it will be understood by those within the art that,
Technical scheme can be modified or equivalent, without deviating from technical solution of the present invention
Objective and scope, it all should be contained in the middle of scope of the presently claimed invention.
Claims (10)
1.HPLC method separation determination levo-cetirizine hydrochloride and the method for enantiomer thereof, it is characterised in that institute
State in method use chromatographic column be with surface chemistry bonding beta-schardinger dextrin-silica gel as filler, use flowing
Phase A and Mobile phase B carry out eluting, enter detector and detect；Described mobile phase A is inorganic salt
Buffer system, described Mobile phase B is organic solvent.
Method the most according to claim 1, it is characterised in that inorganic salt in described inorganic salt buffer system
Concentration is 0.04mol/L-0.06mol/L.
Method the most according to claim 1, it is characterised in that described inorganic salt buffer system is hexafluorophosphoric acid
The buffer system of potassium.
Method the most according to claim 1, it is characterised in that described inorganic salt buffer system pH value is 2-4.
Method the most according to claim 1, it is characterised in that described mobile phase A and the volume of Mobile phase B
Compare 60:40；Described organic solvent includes acetonitrile.
Method the most according to claim 1, it is characterised in that described flow rate of mobile phase is 0.3-0.7ml/min,
Described chromatographic column post case temperature is 20-30 DEG C.
Method the most according to claim 1, it is characterised in that the specification of described chromatographic column is 150 × 6.0mm,
5μm。
Method the most according to claim 1, it is characterised in that the detection wavelength of described detector is
220-240nm。
9. according to the method described in any one of claim 1-8, it is characterised in that specifically include following steps:
1) take the reference substance of levo-cetirizine hydrochloride and enantiomer thereof respectively, make to be measured with diluent dissolving
Sample and the reference substance solution of enantiomer thereof, take testing sample levo-cetirizine hydrochloride and right respectively
Reflect the reference substance solution sample introduction of isomer, carry out efficient liquid phase chromatographic analysis, determine levo-cetirizine hydrochloride
And the retention time of enantiomer；
2) take levo-cetirizine hydrochloride test sample to add diluent and make need testing solution, then take diluent as sky
White solution, takes need testing solution and blank solution sample introduction respectively, carries out efficient liquid phase chromatographic analysis, record
Chromatogram, completes the separation determination of levo-cetirizine hydrochloride and enantiomer thereof.
Method the most according to claim 9, it is characterised in that step 1) described diluent is acetonitrile or acetonitrile
Aqueous dissolution sample, in the aqueous solution of institute's acetonitrile, the volume ratio of acetonitrile and water is 40:60.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610382247.3A CN105954419B (en) | 2016-06-01 | 2016-06-01 | The method of HPLC method separation determination levo-cetirizine hydrochlorides and its enantiomter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610382247.3A CN105954419B (en) | 2016-06-01 | 2016-06-01 | The method of HPLC method separation determination levo-cetirizine hydrochlorides and its enantiomter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105954419A true CN105954419A (en) | 2016-09-21 |
| CN105954419B CN105954419B (en) | 2018-02-06 |
Family
ID=56908301
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610382247.3A Active CN105954419B (en) | 2016-06-01 | 2016-06-01 | The method of HPLC method separation determination levo-cetirizine hydrochlorides and its enantiomter |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105954419B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106769963A (en) * | 2016-12-08 | 2017-05-31 | 湖北远大天天明制药有限公司 | A kind of method for separating and/or detecting lavo-ofloxacin and methyl hydroxybenzoate in lavo-ofloxacin hydrochloride gel for eye |
| CN106996964A (en) * | 2017-04-20 | 2017-08-01 | 山东赛托生物科技股份有限公司 | Method and the application of hydroxypropyl beta cyclodextrin using reversed-phased high performace liquid chromatographic separating chiral enantiomer |
| CN110927308A (en) * | 2019-11-07 | 2020-03-27 | 徐州立兴佳正医药科技有限公司 | Method for determining concentration of cetirizine in blood plasma by liquid chromatography-mass spectrometry |
| WO2020067680A1 (en) * | 2018-09-27 | 2020-04-02 | 주식회사 엘지화학 | Dianhydride analysis method |
| CN110988163A (en) * | 2019-11-29 | 2020-04-10 | 重庆华邦胜凯制药有限公司 | Method for separating and determining levocetirizine hydrochloride and genotoxic impurity E thereof by HPLC method |
| CN112394134A (en) * | 2019-08-14 | 2021-02-23 | 江苏晶立信医药科技有限公司 | Detection method of related substances of cimetidine raw material medicine |
| US11639917B2 (en) | 2018-09-27 | 2023-05-02 | Lg Chem, Ltd. | Dianhydride analysis method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009062036A2 (en) * | 2007-11-09 | 2009-05-14 | Dr. Reddy's Laboratories Ltd. | Processes for preparing levocetirizine and pharmaceutically acceptable salts thereof |
| WO2009061465A1 (en) * | 2007-11-06 | 2009-05-14 | Teva Pharmaceutical Industries Ltd. | Chewable formulations |
-
2016
- 2016-06-01 CN CN201610382247.3A patent/CN105954419B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009061465A1 (en) * | 2007-11-06 | 2009-05-14 | Teva Pharmaceutical Industries Ltd. | Chewable formulations |
| WO2009062036A2 (en) * | 2007-11-09 | 2009-05-14 | Dr. Reddy's Laboratories Ltd. | Processes for preparing levocetirizine and pharmaceutically acceptable salts thereof |
Non-Patent Citations (4)
| Title |
|---|
| Q. LIU，ET AL: "Direct Separation of the Enantiomers of Cetirizine and Related Compounds by Reversed-Phase Chiral HPLC", 《CHROMATOGRAPHIA》 * |
| 洪江游等: "高效液相色谱法测定盐酸左西替利嗪颗粒中的有关物质", 《中国医药指南》 * |
| 王诗卓等: "毛细管电泳法检查盐酸左西替利嗪片中右旋异构体杂质", 《浙江大学学报（医学版）》 * |
| 马仕珉等: "HPLC法测定盐酸左西替利嗪及其片剂中s-异构体", 《药物分析杂志》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106769963A (en) * | 2016-12-08 | 2017-05-31 | 湖北远大天天明制药有限公司 | A kind of method for separating and/or detecting lavo-ofloxacin and methyl hydroxybenzoate in lavo-ofloxacin hydrochloride gel for eye |
| CN106769963B (en) * | 2016-12-08 | 2019-06-25 | 湖北远大天天明制药有限公司 | A method of lavo-ofloxacin and methyl hydroxybenzoate in separation and/or detection lavo-ofloxacin hydrochloride gel for eye |
| CN106996964A (en) * | 2017-04-20 | 2017-08-01 | 山东赛托生物科技股份有限公司 | Method and the application of hydroxypropyl beta cyclodextrin using reversed-phased high performace liquid chromatographic separating chiral enantiomer |
| WO2020067680A1 (en) * | 2018-09-27 | 2020-04-02 | 주식회사 엘지화학 | Dianhydride analysis method |
| US11639917B2 (en) | 2018-09-27 | 2023-05-02 | Lg Chem, Ltd. | Dianhydride analysis method |
| CN112394134A (en) * | 2019-08-14 | 2021-02-23 | 江苏晶立信医药科技有限公司 | Detection method of related substances of cimetidine raw material medicine |
| CN110927308A (en) * | 2019-11-07 | 2020-03-27 | 徐州立兴佳正医药科技有限公司 | Method for determining concentration of cetirizine in blood plasma by liquid chromatography-mass spectrometry |
| CN110988163A (en) * | 2019-11-29 | 2020-04-10 | 重庆华邦胜凯制药有限公司 | Method for separating and determining levocetirizine hydrochloride and genotoxic impurity E thereof by HPLC method |
| CN110988163B (en) * | 2019-11-29 | 2022-04-19 | 重庆华邦胜凯制药有限公司 | Method for separating and determining levocetirizine hydrochloride and genotoxic impurity E thereof by HPLC method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105954419B (en) | 2018-02-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105954419A (en) | Method for separating and determining levocetirizine hydrochloride and enantiomer thereof through HPLC method | |
| Ariza et al. | Tau positron emission tomography (PET) imaging: past, present, and future | |
| Christopher et al. | Biophysical fragment screening of the β1-adrenergic receptor: identification of high affinity arylpiperazine leads using structure-based drug design | |
| CN102276624B (en) | Olanzapine related substance and preparation method as well as high-efficiency liquid-phase chromatographic analysis method thereof | |
| LLerena et al. | Determination of fluoxetine and norfluoxetine in human plasma by high-performance liquid chromatography with ultraviolet detection in psychiatric patients | |
| CN110045038B (en) | Method for separating and determining atorvastatin and related impurities by HPLC (high performance liquid chromatography) method | |
| Yang et al. | GSK1702934A and M085 directly activate TRPC6 via a mechanism of stimulating the extracellular cavity formed by the pore helix and transmembrane helix S6 | |
| Reinartz et al. | Structure-bias relationships for fenoterol stereoisomers in six molecular and cellular assays at the β 2-adrenoceptor | |
| CN103864646B (en) | The impurity preparation of rasagiline mesilate and the method for analysis | |
| CN102952113B (en) | 5,6,7,8-tetrahydro-6-(N,N-di((2-thiophene)ethyl))amino-1-naphthol, preparation method and application thereof | |
| CN108061767A (en) | The method of HPLC method separation determination Rivaroxaban intermediates and its related impurities | |
| CN104764840B (en) | The separation of palonosetron Hcl and impurity and detection method | |
| Xue et al. | A mix-and-click method to measure amyloid-β concentration with sub-micromolar sensitivity | |
| CN104297354B (en) | The detection method of impurity in a kind of high effective liquid chromatography for measuring amyl ethyl quin ether hydrochloride | |
| Brittain | Profiles of drug substances, excipients, and related methodology | |
| CN106018601A (en) | Method for determining related substances in paliperidone raw material | |
| CN105319288A (en) | Method for separating and measuring bilastine and technical impurities in preparation of bilastine | |
| CN110988163B (en) | Method for separating and determining levocetirizine hydrochloride and genotoxic impurity E thereof by HPLC method | |
| CN104422738B (en) | A kind of method separating analysis milrinone | |
| CN114685409B (en) | Escitalopram derivative, immunogen, escitalopram-resistant specific antibody, and preparation method and application thereof | |
| Wang et al. | Plasma protein binding monitoring of therapeutic drugs in patients using single set of hollow fiber centrifugal ultrafiltration | |
| CN102095876A (en) | Method for detecting blood concentration of cyclosporine A | |
| Zagórska et al. | Serotonin transporter activity of imidazolidine-2, 4-dione and imidazo [2, 1-f] purine-2, 4-dione derivatives in aspect of their acid–base properties | |
| CN114685470B (en) | Risperidone key group derivative, immunogen, anti-risperidone specific antibody, and preparation methods and applications thereof | |
| CN114685400B (en) | Key group derivative of aripiprazole, immunogen, anti-aripiprazole specific antibody, and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |