CN105891377A - High-performance liquid chromatography analytical method for istradefylline related substances - Google Patents
High-performance liquid chromatography analytical method for istradefylline related substances Download PDFInfo
- Publication number
- CN105891377A CN105891377A CN201610475927.XA CN201610475927A CN105891377A CN 105891377 A CN105891377 A CN 105891377A CN 201610475927 A CN201610475927 A CN 201610475927A CN 105891377 A CN105891377 A CN 105891377A
- Authority
- CN
- China
- Prior art keywords
- istradefylline
- performance liquid
- liquid chromatography
- hplc
- high performance
- 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)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
The invention discloses a high-performance liquid chromatography analytical method for istradefylline related substances. A reversed phase chromatographic column and an ultraviolet detector are adopted for isocratic elution with acetonitrile-phosphate buffer as a mobile phase. All known impurities in raw materials and preparations of istradefylline can be analyzed simultaneously, contents of the known impurities can be effectively controlled by a main component self contrast method with correction factors, a degree of separation between each impurity peak and a main peak is larger than 1.5, and purity of each impurity peak and the main peak is 1.0. The high-performance liquid chromatography analytical method for the istradefylline related substances is a high-specificity simple analytical method for quality control analysis of the raw materials and the preparations of the istradefylline.
Description
One, technical field
The present invention relates to a kind of analysis method of chemicals purity, a kind of istradefylline has the high-efficient liquid of related substance
Analysis of hplc method.
Two, background technology
Istradefylline (Istradefylline), chemistry entitled (E)-8-(3,4-dimethoxy-styryl)-1,3-diethyl-7-first
Base-3,7-dihydro-1H-purine-2,6-diketone, chemical structural formula is as follows:
Istradefylline is a kind of selective adenosine A 2 A receptor antagonists, by the exploitation of Japan Kyowa Hakko Kirin company.
Istradefylline sheet (trade name Nouriast, specification 20mg) obtains Japan PMDA approval listing in March, 2013, faces
Bed, for treating parkinson disease and improving the dyskinesia at parkinsonism initial stage, is particularly suited for improving because of levodopa
The agent end phenomenon that treatment causes.
Istradefylline impurity is more, and from structure, impurity is mainly derived from substituted purin mother nucleus structure and changes and side base benzene second
Alkene structural isomerismization is relevant, and impurity is respectively provided with styryl structures, and the close impurity of polarity is many；In terms of source, istradefylline raw material
Impurity be mainly derived from building-up process introduce reaction raw materials (impurity H), synthetic intermediate (impurity D), reaction by-product
Thing (impurity E, impurity F, impurity G) and degradation impurity (impurity A, impurity B, impurity C), istradefylline preparation miscellaneous
Matter derives from raw material and introduces impurity (impurity D, impurity E, impurity F, impurity G, impurity H), process contaminants (impurity B)
And degradation impurity (impurity A, impurity B, impurity C).
Set up the literary composition that the analysis method of the istradefylline raw material on the basis of comprehensive impurity analysis of spectrum and preparation thereof is not the most relevant at present
Offer report.
Three, summary of the invention
The present invention is directed to existing document to istradefylline raw material and the disappearance of preparation impurity identification research thereof, it is desirable to provide a kind of Yi Qu
Theophylline has the HPLC (high performance liquid chromatography) of related substance.The present invention is miscellaneous to istradefylline by process trial, pressure Degrading experiment
Matter carries out being enriched with, separating-purifying, identifies 8 main known impurities, and impurity has been carried out ownership of tracing to the source, including Yi Qu
Theophylline reaction raw materials (impurity H), synthetic intermediate (impurity D), istradefylline synthesising by-product are (impurity E, impurity F, miscellaneous
Matter G) and degradation impurity (impurity A, impurity B, impurity C).
Inventor attempts to by C18 (150 × 4.6mm, 5 μm) the chromatographic column each known impurities of separation, but each impurity and main constituent
Baseline separation can not be reached, improper.Therefore, the chromatographic column using C18 (250 × 4.6mm, 5 μm) instead separates, through right
Flowing phase composition and the optimal screening of ratio, determine the analysis method of the present invention.Press Chinese Pharmacopoeia four general rules of version in 2015 simultaneously
<0512>(high performance liquid chromatography) and general rule<9101>(drug standard analyze method validation guideline) definition and
Verification method, carries out specificity checking, result show the method can analyze simultaneously in istradefylline raw material and preparation thereof all
Know impurity, and can effectively control each known impurity level by the main composition Self-control method of the correction up factor, each impurity peaks with
Separating degree between main peak is more than 1.5, and main peak and each impurity peaks peak purity are 1.0.
Described peak purity refers to use the photodiode array detector being furnished with corresponding analysis software, gathers, records, analyzes through color
The spectroscopic data of spectrum post separation component, the conforming weighted value of spectral signature that the sign particular separation component that automatically generates is corresponding.
Istradefylline of the present invention has the HPLC (high performance liquid chromatography) of related substance, uses reversed phase chromatographic column and UV-detector, is
With the mixed solution of acetonitrile-phosphate buffer for flowing phase, carry out isocratic elution, comprise the steps:
(1) sample preparation: take istradefylline raw material or powder formulation, with the mixed liquor ultrasonic dissolution of acetonitrile and phosphate buffer,
Filter or centrifugal, be configured to the istradefylline solution that concentration is 0.1-1.5mg/ml；
(2) chromatographic condition is arranged: using anti-phase C18 post, column temperature is arranged on 20-50 DEG C；With acetonitrile and phosphate buffer
Mixed liquor is flowing phase, carries out isocratic elution；Flow velocity is 0.5-2.0ml/min；Detection wavelength is 210-270nm；
(3) detection: take the istradefylline solution that step (1) is prepared, sample introduction 10-50 μ l, record chromatogram.
In step (2) anti-phase C18 post selected from Grace Smart C18 (250 × 4.6mm, 5 μm), Agilent C18 (250 × 4.6mm,
5 μm) or Diamonsil C18 (250 × 4.6mm, 5 μm), preferably Diamonsil C18 (250 × 4.6mm, 5 μm).
In the mixed liquor of step (1) acetonitrile and phosphate buffer, acetonitrile is 1: 1 with the volume ratio of phosphate buffer.
In step (2) flowing mutually, acetonitrile is 50: 49-54 with the volume ratio of phosphate buffer, preferably 50: 50.
In step (1) or step (2), phosphate buffer used is the aqueous solution of potassium dihydrogen phosphate, the concentration of potassium dihydrogen phosphate
For 0.01-0.5mol/L, preferably 0.05mol/L, with potassium hydroxide tune pH value to 5.0-7.0, preferably 5.9-6.3.
In step (2), flow velocity is 0.8-1.2ml/min, and detection wavelength is 225-235nm.
In step (3), sample size is 20 μ l.
Using the inventive method to efficiently control and have related substance in istradefylline raw material and preparation, 8 known impurities all can be
Analyzing out on one collection of illustrative plates, the separating degree between each impurity peaks and main peak is more than 1.5, and main peak is with each impurity peaks peak purity
1.0.Analysis process is shown in that embodiment 1, typical color spectrogram are shown in that Fig. 1, result of calculation are shown in Table 1.
Table 1 istradefylline and each known impurities chromatographic isolation parametric results
| Title | Relative retention time | Separating degree | The peak purity factor |
| Impurity H | 0.19 | / | 1.0 |
| Impurity G | 0.23 | 3.329 | 1.0 |
| Impurity F | 0.36 | 4.813 | 1.0 |
| Impurity C | 0.39 | 2.095 | 1.0 |
| Impurity D | 0.51 | 7.765 | 1.0 |
| Impurity E | 0.52 | 0.715 | 1.0 |
| Impurity A | 0.68 | 8.233 | 1.0 |
| Istradefylline | 1.00 | 13.223 | 1.0 |
| Impurity B | 1.21 | 6.281 | 1.0 |
Using the inventive method can analyze istradefylline degradation impurity under various complex environments, method specificity is strong.In pressing
State's pharmacopeia four general rules<0512>(high performance liquid chromatography) of version in 2015 and general rule<9101>(drug standard analysis side
Method verification guide principle) definition and verification method, by istradefylline raw material or powder formulation respectively with acid, alkali, high temperature, oxygen
Change, illumination destroys, and prepares and destroys sample, gathers each destruction sample chromatogram figure by the inventive method respectively, and analysis process is shown in enforcement
Example 2, typical color spectrogram is shown in Fig. 2-7.Result shows that the method can analyze the sample destroyed through acid, alkali, high temperature, oxidation, illumination
Product, main peak and each impurity peaks all can reach baseline separation, and main peak purity is 1.0.
Use the inventive method each known impurities can be carried out quantitative analysis.(high by Chinese Pharmacopoeia four general rules of version in 2015 0512
Effect liquid phase chromatogram method) and the definition of general rule 9101 (drug standard analyzes method validation guideline) and verification method, adopt
Detecting detection limit, the quantitative limit of 8 known impurities of istradefylline with impurity counter point, result shows that the method is to each miscellaneous
The response value of matter is high, can effectively control each known impurities, the results are shown in Table 2.
Table 2 istradefylline and known impurities quantitative analysis certificate parameter result thereof
Istradefylline raw material and preparation impurity thereof are traced to the source ownership by the present invention first, identify 8 known impurities, for Yi Qu
Theophylline raw material and preparation thereof have related substance research to provide the spectrum reference of reliable impurity, have the most progressive bigger effect and reality
Using value.
Four, accompanying drawing explanation
Fig. 1 is the mixed chromatogram of embodiment 1 istradefylline and known impurities.
Fig. 2 is that embodiment 2 acid destroys chromatogram.
Fig. 3 is that embodiment 2 alkali destroys chromatogram.
Fig. 4 is embodiment 2 high temperature chromatogram.
Fig. 5 is embodiment 2 Oxidative demage chromatogram.
Fig. 6 is that embodiment 2 illumination destroys chromatogram.
Fig. 7 is that embodiment 2 istradefylline sheet does not destroys sample chromatogram figure.
Fig. 8 is that embodiment 3 istradefylline has related substance chromatogram.
Using the present invention to analyze method location known impurities (impurity A-H, Fig. 1), main peak all can reach baseline and divide with each impurity peaks
From.Use the present invention to analyze method istradefylline and tablet has related substance, result istradefylline raw material only to detect trace impurity B
(retention time: 14.160min, Fig. 8), istradefylline sheet then detects trace impurity B and 1 unknown impuritie (retention time
It is followed successively by: 13.935min, 7.073min, Fig. 7).Use the present invention analyze method investigate istradefylline formulation samples acid, alkali,
Catabolite under the influence of the factors such as high temperature, illumination, oxidation, compares with sample before degraded, and result shows that this product is to acid, high temperature
More stable, acid destroys only detection trace impurity A and impurity B (retention time is followed successively by: 7.898min, 13.949min, Fig. 2),
High temperature only detects trace impurity B and 1 unknown impuritie (retention time is followed successively by: 13.896min, 7.027min, Fig. 4)；
This product is unstable under alkali, light, oxidizing condition, and wherein alkali destroys detection impurity A (retention time: 7.909min), impurity B
(retention time: 13.962min), impurity C (retention time: 4.560min) and 1 unknown impuritie (Fig. 3), photo damage
Detection impurity A (retention time: 7.889min), impurity B (retention time: 13.915min), impurity C (retention time:
4.564min) He 1 unknown impuritie (Fig. 3), Oxidative demage detection impurity B (retention time: 13.984min), impurity C
(retention time: 4.563min) and 3 unknown impurities (Fig. 5).
Five, detailed description of the invention
Embodiment 1:
Detecting instrument and chromatographic condition:
High performance liquid chromatograph: Agilent PUMP, Agilent DAD detector
Chromatographic column: Diamonsil C18 chromatographic column (250 × 4.6mm, 5 μm)；Flowing phase: volume ratio is the acetonitrile of 50: 50
-0.05mol/L phosphate buffer (potassium hydroxide tune pH value to 6.1)；Detection wavelength: 230nm；Flow velocity: 1.0ml/min；
Sample size: 20 μ l.
Experimental procedure:
(1) sample preparation:
Take istradefylline, known impurities A-H each in right amount, (take biphosphate with the acetonitrile-phosphate buffer of volume ratio 1: 1
Potassium 6.8g, the 1000ml that adds water make dissolving, with potassium hydroxide regulation pH value to 6.1) ultrasonic dissolution dilution make containing Yi Qucha
Alkali about 0.5mg/ml, impurity A-H are each about the solution of 5 μ g/ml, as sample solution.
(2) detection: take above-mentioned sample solution, sample introduction 20 μ l, record chromatogram.
Typical color spectrogram is shown in Fig. 1.
Embodiment 2:
Detecting instrument and chromatographic condition:
High performance liquid chromatograph: Agilent PUMP, Agilent DAD detector
Chromatographic column: Diamonsil C18 chromatographic column (250 × 4.6mm, 5 μm)；Flowing phase: with embodiment 1；Detection wavelength:
230nm；Flow velocity: 1.0ml/min.
(1) sample preparation:
Acid destroys: take istradefylline sheet, finely ground, takes fine powder appropriate (being approximately equivalent to containing istradefylline 10mg), puts 20ml brown
In measuring bottle, add 1mol/L hydrochloric acid solution 2ml, put 60 DEG C of water-baths 2 hours, take out, let cool, add 1mol/L sodium hydroxide molten
Liquid 2ml, with the acetonitrile-phosphate buffer of volume ratio 1: 1, (taking potassium dihydrogen phosphate 6.8g, the 1000ml that adds water makes dissolving, uses
Potassium hydroxide regulation pH value is to 6.1) dissolve and be diluted to scale, shake up, filter, destroy sample as acid.
Alkali destroys: take istradefylline sheet, finely ground, takes fine powder appropriate (being approximately equivalent to containing istradefylline 10mg), puts 20ml brown
In measuring bottle, add 1mol/L sodium hydroxide solution 2ml, put 60 DEG C of water-baths 2 hours, take out, let cool, add 1mol/L hydrochloric acid molten
Liquid 2ml, with the acetonitrile-phosphate buffer of volume ratio 1: 1, (taking potassium dihydrogen phosphate 6.8g, the 1000ml that adds water makes dissolving, uses
Potassium hydroxide regulation pH value is to 6.1) dissolve and be diluted to scale, shake up, filter, destroy sample as alkali.
High temperature: take istradefylline sheet, finely ground, heat 3 hours in 150 DEG C, take fine powder and (be approximately equivalent to containing Yi Qu in right amount
Theophylline 10mg), put in 20ml brown measuring bottle, with the acetonitrile-phosphate buffer of volume ratio 1: 1 (take potassium dihydrogen phosphate 6.8g,
The 1000ml that adds water makes dissolving, with potassium hydroxide regulation pH value to 6.1) dissolve and be diluted to scale, shake up, filter, as
High temperature sample.
Oxidative demage: take istradefylline sheet, finely ground, take fine powder appropriate (being approximately equivalent to containing istradefylline 10mg), put 20ml
In brown measuring bottle, add 30% hydrogenperoxide steam generator 2ml, put 60 DEG C of water-baths 2 hours, take out, let cool, by volume ratio 1: 1
Acetonitrile-phosphate buffer (taking potassium dihydrogen phosphate 6.8g, the 1000ml that adds water makes dissolving, with potassium hydroxide regulation pH value extremely
6.1) dissolve and be diluted to scale, shaking up, filtering, as Oxidative demage sample.
Photo damage: take istradefylline sheet, finely ground, take fine powder appropriate (being approximately equivalent to containing istradefylline 10mg), put 20ml brown
In measuring bottle, with the acetonitrile-phosphate buffer of volume ratio 1: 1, (taking potassium dihydrogen phosphate 6.8g, the 1000ml that adds water makes dissolving, uses
Potassium hydroxide regulation pH value is to 6.1) dissolve and be diluted to scale, put and irradiate 72 hours under high light (10000Lx), shake up,
Filter, as photo damage sample.
Do not destroy: take istradefylline sheet, finely ground, take fine powder appropriate (being approximately equivalent to containing istradefylline 10mg), put 20ml brown
In measuring bottle, with the acetonitrile-phosphate buffer of volume ratio 1: 1, (taking potassium dihydrogen phosphate 6.8g, the 1000ml that adds water makes dissolving, uses
Potassium hydroxide regulation pH value is to 6.1) dissolve and be diluted to scale, shake up, filter, as not destroying sample.
(2) detection: take above-mentioned each sample solution, sample introduction 20 μ l, records chromatogram respectively respectively.
Typical color spectrogram is shown in Fig. 2-7.
Embodiment 3:
Detecting instrument and chromatographic condition:
High performance liquid chromatograph: Agilent PUMP, Agilent DAD detector
Chromatographic column: Diamonsil C18 chromatographic column (250 × 4.6mm, 5 μm)；Flowing phase: volume ratio is the acetonitrile of 50: 50
-0.05mol/L phosphate buffer (potassium hydroxide tune pH value to 6.1)；Detection wavelength: 230nm；Flow velocity: 1.0ml/min；
Sample size: 20 μ l.
Experimental procedure:
(1) sample preparation: take istradefylline appropriate, with the acetonitrile-0.05mol/L phosphate buffer (hydrogen of volume ratio 1: 1
Potassium oxide adjusts pH value to 6.1) dissolve and dilute the solution made in every 1ml containing about 0.5mg, shake up, as sample solution.
(2) detection: take above-mentioned sample solution, sample introduction 20 μ l, record chromatogram.
Typical color spectrogram is shown in Fig. 8.
Claims (10)
1. an istradefylline has the HPLC (high performance liquid chromatography) of related substance, it is characterised in that comprise the steps:
(1) sample preparation: take istradefylline raw material or powder formulation, with the mixed liquor ultrasonic dissolution of acetonitrile and phosphate buffer,
Filter or centrifugal, be configured to the istradefylline solution that concentration is 0.1-1.5mg/ml；
(2) chromatographic condition is arranged: using anti-phase C18 post, column temperature is arranged on 20-50 DEG C；With acetonitrile and phosphate buffer
Mixed liquor is flowing phase, carries out isocratic elution；Flow velocity is 0.5-2.0ml/min；Detection wavelength is 210-270nm；
(3) detection: take the istradefylline solution that step (1) is prepared, sample introduction 10-50 μ l, record chromatogram.
HPLC (high performance liquid chromatography) the most according to claim 1, it is characterised in that:
In step (2) anti-phase C18 post selected from Grace Smart C18 (250 × 4.6mm, 5 μm), Agilent C18 (250 × 4.6mm,
5 μm) or Diamonsil C18 (250 × 4.6mm, 5 μm).
HPLC (high performance liquid chromatography) the most according to claim 1 and 2, it is characterised in that:
In step (2), anti-phase C18 post is Diamonsil C18 (250 × 4.6mm, 5 μm).
HPLC (high performance liquid chromatography) the most according to claim 1, it is characterised in that:
In the mixed liquor of step (1) acetonitrile and phosphate buffer, acetonitrile is 1: 1 with the volume ratio of phosphate buffer.
HPLC (high performance liquid chromatography) the most according to claim 1, it is characterised in that:
In step (2) flowing mutually, acetonitrile is 50: 49-54 with the volume ratio of phosphate buffer.
HPLC (high performance liquid chromatography) the most according to claim 1 or 5, it is characterised in that:
In step (2) flowing mutually, acetonitrile is 50: 50 with the volume ratio of phosphate buffer.
HPLC (high performance liquid chromatography) the most according to claim 1, it is characterised in that:
Described phosphate buffer is the aqueous solution of potassium dihydrogen phosphate, and the concentration of potassium dihydrogen phosphate is 0.01-0.5mol/L, uses hydrogen-oxygen
Changing potassium adjusts pH value to 5.0-7.0.
HPLC (high performance liquid chromatography) the most according to claim 7, it is characterised in that:
In described phosphate buffer, the concentration of potassium dihydrogen phosphate is 0.05mol/L, with potassium hydroxide tune pH value to 5.9-6.3.
HPLC (high performance liquid chromatography) the most according to claim 1, it is characterised in that:
In step (2), flow velocity is 0.8-1.2ml/min, and detection wavelength is 225-235nm.
HPLC (high performance liquid chromatography) the most according to claim 1, it is characterised in that:
In step (3), sample size is 20 μ l.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610475927.XA CN105891377B (en) | 2016-06-24 | 2016-06-24 | A kind of HPLC analytical method of istradefylline about material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610475927.XA CN105891377B (en) | 2016-06-24 | 2016-06-24 | A kind of HPLC analytical method of istradefylline about material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105891377A true CN105891377A (en) | 2016-08-24 |
| CN105891377B CN105891377B (en) | 2018-01-30 |
Family
ID=56718293
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610475927.XA Active CN105891377B (en) | 2016-06-24 | 2016-06-24 | A kind of HPLC analytical method of istradefylline about material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105891377B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106478673A (en) * | 2016-10-11 | 2017-03-08 | 合肥久诺医药科技有限公司 | A kind of preparation method of istradefylline contamination levels product |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016003186A (en) * | 2014-06-13 | 2016-01-12 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | Phthalan ring-containing adenosine A2A receptor antagonist |
| CN105534928A (en) * | 2015-12-18 | 2016-05-04 | 北京万全德众医药生物技术有限公司 | Orally disintegrating tablet containing Istradefylline and preparation method thereof |
-
2016
- 2016-06-24 CN CN201610475927.XA patent/CN105891377B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016003186A (en) * | 2014-06-13 | 2016-01-12 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | Phthalan ring-containing adenosine A2A receptor antagonist |
| CN105534928A (en) * | 2015-12-18 | 2016-05-04 | 北京万全德众医药生物技术有限公司 | Orally disintegrating tablet containing Istradefylline and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| N. RAO等: "A Study of the Pharmacokinetic Interaction of Istradefylline, a Novel Therapeutic for Parkinson’s Disease, and Atorvastatin", 《J CLIN PHARMACOL》 * |
| 龚登凰等: "伊曲茶碱的合成工艺改进", 《精细化工中间体》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106478673A (en) * | 2016-10-11 | 2017-03-08 | 合肥久诺医药科技有限公司 | A kind of preparation method of istradefylline contamination levels product |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105891377B (en) | 2018-01-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103743826B (en) | A kind of HPLC analytical method of Azilsartan | |
| CN105158358B (en) | The method for detecting the 42 kinds of chemicals illegally added in Chinese patent drug and health products simultaneously | |
| Jiang et al. | Development and validation of sensitive LC-MS/MS assays for quantification of HP-# x03B2;-CD in human plasma and CSF | |
| CN111487354B (en) | Method for detecting cefixime related impurities | |
| Ma et al. | Ultrafast polyphenol metabolomics of red wines using MicroLC-MS/MS | |
| CN105388244B (en) | A kind of ACT-064992 is about the HPLC (high performance liquid chromatography) of material | |
| CN110320290A (en) | HPLC detection method of the Mecobalamin injection in relation to substance | |
| CN107529337A (en) | The HPLC analyses of impurity in two to the water wei ling alcohol | |
| CN104597192A (en) | Method for detecting clevidipine butyrate and related substances in preparations of clevidipine butyrate | |
| CN105866298A (en) | High performance liquid chromatography analyzing method of eplerenone related substances | |
| Pourbasheer et al. | Dispersive liquid–liquid microextraction for preconcentration and determination of phenytoin in real samples using response surface methodology-high performance liquid chromatography | |
| Antil et al. | UPLC method for simultaneous determination of valsartan & hydrochlorothiazide in drug products | |
| Avula et al. | Analysis of primaquine and its metabolite carboxyprimaquine in biological samples: enantiomeric separation, method validation and quantification | |
| CN105891377A (en) | High-performance liquid chromatography analytical method for istradefylline related substances | |
| CN104280473B (en) | The analytical approach of 5 hydroxymethyl furfural in a kind of Linezolid Injection | |
| Jiang et al. | In-line spectroscopy combined with multivariate analysis methods for endpoint determination in column chromatographic adsorption processes for herbal medicine | |
| Pinto et al. | Development and validation of a stability‐indicating HPLC method for topiramate using a mixed‐mode column and charged aerosol detector | |
| CN104764840B (en) | The separation of palonosetron Hcl and impurity and detection method | |
| CN107085053A (en) | The analysis method of perchlorate, kit and its application in reconstituted tobacoo | |
| Čarapić et al. | Ultra‐performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities | |
| CN105866290B (en) | A kind of HPLC analytical methods of Rui Jianuosheng in relation to material | |
| Rejent et al. | Diazepam abuse: incidence, rapid screening, and confirming methods. | |
| Lu et al. | Development of a UPLC–MS/MS method for simultaneous therapeutic drug monitoring of anti-hepatocellular carcinoma drugs and analgesics in human plasma | |
| CN108490095A (en) | A kind of method of Multiple components assay in pilose gerbera herb medicinal material | |
| CN105866297A (en) | High performance liquid chromatography method of pomalidomide related substance |
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 |