CN104749289A - Method for detecting and separating pomalidomide related substances by use of high performance liquid chromatography - Google Patents
Method for detecting and separating pomalidomide related substances by use of high performance liquid chromatography Download PDFInfo
- Publication number
- CN104749289A CN104749289A CN201510182078.4A CN201510182078A CN104749289A CN 104749289 A CN104749289 A CN 104749289A CN 201510182078 A CN201510182078 A CN 201510182078A CN 104749289 A CN104749289 A CN 104749289A
- Authority
- CN
- China
- Prior art keywords
- mobile phase
- acetonitrile
- degree amine
- horse degree
- detection 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
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention discloses a method for detecting and separating pomalidomide or related substances in an oral solid preparation by use of high performance liquid chromatography. The detection method comprises the following steps: (1) preparing a system adaptability solution; (2) carrying out system adaptability testing; (3) preparing a test solution; and (4) determining according to the following high performance liquid chromatography conditions: ion pair phosphate buffer-acetonitrile is used as a moving phase A, and methanol-acetonitrile is used as a moving phase B for gradient elution; the detection wavelength of an ultraviolet detector is 200-400nm; and a chromatographic column takes octadecyl silane bonded silica gel as a filling agent, the flowing rate is 0.5-2.0ml/min, and the column temperature is 10-60 DEG C. The method solves the problem of effective detection and separation of pomalidomide or related substances in the oral solid preparation.
Description
Technical field
The invention belongs to Pharmaceutical Analysis technical field, in particular, relate to a kind of high performance liquid chromatography and be separated the method detecting its related substances in pool horse degree amine or its oral solid formulation.
Background technology
Pool horse degree amine, Pomalidomide, chemical name: (RS)-4-amino-2-(2,6-dioxo-piperidin-3-base)-isoindoline-1,3 – diketone, chemical constitution:
Pool horse degree amine is a kind of new immunomodulator, and belonging to thalidomide analogs, is the immunomodulator of the 3rd listing after Thalidomide (thalidomide), lenalidomide (lenalidomide).
Pool horse degree amines is first public in R L Smith et al, Symp.Embryopathic Act.Drugs, (1965), 194-209.
Chinese patent application CN103645259A discloses the method for a kind of Simultaneously test pool horse degree amine and related substance thereof, and the method adopts high performance liquid chromatography to be separated pool horse degree amine and related substance thereof; Wherein apply 18 alkyl silica gel bonded chromatographic post, mobile phase is methyl alcohol: aqueous acetic acid.In described high performance liquid chromatography, flow velocity is 0.5 ~ 1.2ml/min; In described high performance liquid chromatography, determined wavelength is 226nm.The method is simple, convenient, practical, the object that Simultaneously test is separated pool horse degree amine related substance can be reached fast, and the molecular weight that LC-MS (LC-MS) determines unknown impuritie can be applied to, for inferring that the structure of unknown impuritie provides reliable basis, be convenient to the quality control of mooring horse degree amine raw material and preparation.In addition, this patented claim also discloses a kind of application mobile phase A in comparative example: methyl alcohol/Mobile phase B: the chromatographic condition of 25mM ammonium acetate (add formic acid and adjust pH=5.5) detects the method for pool horse degree amine.
Summary of the invention
The present inventor develops a kind of high-efficiency liquid chromatography method for detecting mooring horse degree amine or its oral solid formulation through great many of experiments, effectively can be separated the content of the related substance detected in pool horse degree amine or its oral solid formulation.
The object of this invention is to provide a kind of high-efficiency liquid chromatography method for detecting mooring related substance separation detection in horse degree amine or its oral solid formulation.
Specifically, the invention provides a kind of high-efficiency liquid chromatography method for detecting mooring horse degree amine or its oral solid formulation, this detection method comprises the steps:
(1) compounding system adaptability solution;
(2) system suitability test is carried out;
(3) test solution is prepared;
(4) measure according to following high-efficient liquid phase chromatogram condition:
Mobile phase: with ion pair phosphate buffer-acetonitrile for mobile phase A take methanol-acetonitrile as Mobile phase B;
UV-detector: determined wavelength is 200 ~ 400nm preferably, is 200 ~ 240nm, and most preferably, determined wavelength is 215nm;
Chromatographic column: take octadecylsilane chemically bonded silica as filling agent, theoretical cam curve calculates by pool horse degree amine, is not less than 2000, is preferably not less than 5000, and the tailing factor of pool horse degree amine is less than 2.0, is preferably less than 1.5; More preferably, chromatographic column is that Inertsil ODS 3V series or Luna are serial, particularly preferably, Inertsil ODS-3, packing material size 5um, the length of chromatographic column is 250mm, and chromatographic column internal diameter is 4.6mm; Or Luna 5u C18100A post;
Flow velocity: 0.5-2.0ml/min, preferably, 1.0ml/min;
Column temperature: 10 ~ 60 DEG C preferably, is 20 ~ 40 DEG C, more preferably, is 25 DEG C.
In embodiments of the invention, the high-efficiency liquid chromatography method for detecting of pool horse degree amine provided by the invention or its oral solid formulation, wherein, the preparation of described system suitability solution refers to that precision takes pool horse degree amine, pool horse degree amine impurity, add 40 volume % acetonitrile solutions to dissolve and dilute and make about containing pool horse degree amine 0.2mg/ml, about containing the solution of pool horse degree amine impurity 0.2 μ g/ml, as system suitability solution.
In embodiments of the invention, the high-efficiency liquid chromatography method for detecting of pool horse degree amine provided by the invention or its oral solid formulation, wherein, described system suitability refers to gets system suitability solution 20 μ l injection liquid chromatography, between pool horse degree amine and its each impurity, degree of separation should conform with the regulations, each impurity can detect, and theoretical cam curve calculates by pool horse degree amine, should be not less than 3000; The tailing factor of pool horse degree amine must not be greater than 2.0
In embodiments of the invention, the high-efficiency liquid chromatography method for detecting of pool horse degree amine provided by the invention or its oral solid formulation, wherein, carries out gradient elution with mobile phase A and Mobile phase B.
In embodiments of the invention, the high-efficiency liquid chromatography method for detecting of pool horse degree amine provided by the invention or its oral solid formulation, wherein, and described mobile phase A, described ion pair is selected from alkyl sodium sulfonate, is preferably perfluorooctane sulfonate; The pH of described ion pair phosphate buffer is 2.0-8.0, and preferably pH value is 3.0; The volume ratio of described ion pair phosphate buffer and acetonitrile is 0-100:100-0; Preferably, with perfluorooctane sulfonate 1.08g, phosphoric acid 0.5ml, is diluted with water to 1000ml, regulates pH to 3.0-acetonitrile (volume ratio 90:10) to be mobile phase A with NaOH; Described Mobile phase B, the volume ratio of methyl alcohol and acetonitrile is 0-100:100-0, and preferably, the volume ratio of methyl alcohol and acetonitrile is 50:50.
In a kind of preferred embodiment of the present invention, the invention provides a kind of high-efficiency liquid chromatography method for detecting mooring horse degree amine or its oral solid formulation, wherein, the high-efficient liquid phase chromatogram condition of this detection method comprises:
Mobile phase: with perfluorooctane sulfonate phosphate buffer-acetonitrile for mobile phase A, take methanol-acetonitrile as Mobile phase B, carries out gradient elution; Particularly preferably, with perfluorooctane sulfonate 1.08g, phosphoric acid 0.5ml, is diluted with water to 1000ml, and regulating pH to 3.0 to be perfluorooctane sulfonate phosphate buffer with NaOH, is that the perfluorooctane sulfonate phosphate buffer-acetonitrile of 90:10 is as mobile phase A with volume ratio; Take volume ratio as the methanol-acetonitrile of 50:50 be Mobile phase B, carry out gradient elution;
UV-detector: determined wavelength is 200 ~ 400nm preferably, is 200 ~ 240nm, and most preferably, determined wavelength is 215nm;
Chromatographic column: the chromatographic column taking octadecylsilane chemically bonded silica as filling agent, theoretical cam curve calculates by pool horse degree amine, is not less than 2000, is preferably not less than 5000; The tailing factor of pool horse degree amine is less than 2.0, preferably, is less than 1.5; Preferably, chromatographic column is that Inertsil ODS 3V series or Luna are serial, and particularly preferably, be Inertsil ODS-3, packing material size 5um, the length of chromatographic column is 250mm, and chromatographic column internal diameter is 4.6um; Or Luna 5u C18100A post;
Flow velocity: 0.5-2.0ml/min, preferably, 1.0ml/min;
Column temperature: 10 ~ 60 DEG C preferably, is 20 ~ 40 DEG C, more preferably, is 25 DEG C.
In embodiments of the invention, the invention provides a kind of high-efficiency liquid chromatography method for detecting mooring horse degree amine or its oral solid formulation, wherein, described preparation test solution, can comprise preparation pool horse degree amine impurity reference substance solution, need testing solution and contrast solution:
Impurity reference substance solution
Precision takes CAV23-IMP01 respectively, CAV23-IMP02, CAV23-IMP03, CAV23-IMP04, CAV23-IMP05, and CAV23-IMP06, adds 40 volume % acetonitrile solutions and dissolves and dilute the solution made and about contain 0.2 μ g/ml, as impurity contrast solution;
Need testing solution
Precision takes pool horse degree amine or pool horse degree amine oral solid formulation content, and add 40% acetonitrile solution ultrasonic dissolution, make about containing the solution of pool horse degree amine (PMDA) 0.2mg in every 1ml, filtration, gets subsequent filtrate in right amount as need testing solution.
Contrast solution
Precision measures 1ml need testing solution, puts in 100ml measuring bottle, is diluted to scale, shakes up, in contrast solution with 40% acetonitrile solution.
Precision measures impurity reference substance solution, need testing solution and each 20 μ l of contrast solution, and injection liquid chromatography, carries out wash-out according to following table gradient respectively, record chromatogram, and preferably, record chromatogram is to 50min.
In embodiments of the invention, the high-efficiency liquid chromatography method for detecting of pool horse degree amine provided by the invention or its oral solid formulation, wherein, as aobvious impurity peaks in the chromatogram of need testing solution, except CAV23-IMP01, CAV23-IMP02, CAV23-IMP03, CAV23-IMP04, CAV23-IMP05, CAV23-IMP06 with calculated by peak area, must not cross 0.15% by external standard method, other single impurity peak area must not be greater than 0.1 times of contrast solution major component peak area, and total impurities must not cross 1.0%:
Computing formula:
Amount (the %)=A ' of unknown impuritie
x/ A
t
Total impurities (%)=∑ i
In formula: A
rfor the peak area of reference substance; A
xfor the peak area of known impurities
C
rfor the concentration of reference substance; C
xfor the concentration of known impurities
A '
xfor the peak area of unknown impuritie; A
tfor contrast solution peak area
In embodiments of the invention, pool horse degree amine can adopt WO9320097, and the existing disclosed technology such as WO9509178, CN200580036044.9, CN201210078438.2 obtains.In embodiments of the invention, described pool horse degree amine or its oral solid formulation include but not limited to compound as shown in the table.
In embodiments of the invention, described pool horse degree amine oral solid formulation can be selected from capsule, tablet or solid particle agent, preferably, is capsule.
Pool horse degree amine capsule can adopt following pool horse degree amine capsule: it comprises 1mg, 2mg, 3mg, 4mg tetra-kinds of specifications, and often kind of specification is all by being prepared from forming of weight proportion:
The preparation method of the pool horse degree amine capsule of above-mentioned four kinds of specifications, comprises the steps:
1) pregelatinized starch puts into drying box, dries to moisture≤2.0% for 105 DEG C, for subsequent use;
2) sweet mellow wine is crushed to 80 orders, for subsequent use;
3) take the pregelatinized starch of recipe quantity pool horse degree amine and 50% recipe quantity respectively, mix, obtain potpourri 1;
4) take sweet mellow wine and the residue 50% recipe quantity pregelatinized starch of recipe quantity respectively, cross 80 mesh sieves and mix to obtain potpourri 2;
5) by step 3) potpourri 1 that obtains adds step 4) in the potpourri 2 that obtains, add the sodium stearyl fumarate mixing of recipe quantity;
6) intermediates content uniformity coefficient and content is detected;
7) loading of capsule is calculated according to intermediates content, filled capsules.
Compared with prior art, detection method of the present invention can detect the related substance in pool horse degree amine raw material or preparation effectively, and can be separated with other inactive substances by pool horse degree amine well, can measure the content of its impurity exactly, auxiliary material is Interference Detection not.Meanwhile, the method has simple and fast, favorable reproducibility, and sensitivity for analysis is high, the feature that specificity is strong.
Accompanying drawing explanation
What Fig. 1 represented is typical system suitability chromatogram.
What Fig. 2 represented is typical impurity contrast color spectrogram.
What Fig. 3 represented is typically moor horse degree amine chromatogram.
Embodiment
Further illustrate embodiment of the present invention below by embodiment, protection scope of the present invention is not limited to these embodiments, and those skilled in the art carry out equivalent substitutions and modifications and still belong in the protection domain of the application according to prior art.
Preparation example
The preparation of 3-nitrophthalic acid acid anhydride
In reaction bulb, add ethyl acetate (150ml), 3-nitrophthalic acid (150g), stir.Temperature control less than 50 DEG C slowly adds aceticanhydride (150ml).Finish, 60 DEG C of insulation reaction 3 hours.
In reactant liquor, slowly add normal hexane (750ml), stir cooling growing the grain.Suction filtration.Drying obtains light yellow solid object 125g.
The preparation of 3-nitro-N-(2,6-dioxo-3-piperidyl) phthalimide
Add in reaction bulb DMF (dimethyl formamide) (300ml), 3-nitrophthalic acid acid anhydride (125g), 3-amino piperidine-2,6-dione hydrochloride (95g), anhydrous sodium acetate (40g), stirs and is warming up to 75 ~ 85 DEG C of insulation reaction 6 hours.Reaction Bi Jiangwen adds water growing the grain.Suction filtration, dry gray solid object 140g.
The preparation of pool horse degree amine
THF (1000ml) is added in reaction bulb, methyl alcohol (250ml), 3-nitro-N-(2,6-dioxo-3-piperidyl) phthalimide (140g), 7.5%Pd-C (40g), ammonium formate (150g).Finish, temperature control 20 DEG C of insulation reaction 6 hours.Suction filtration, adds DMF (2000ml), stirring and dissolving, suction filtration in filter cake, and filtrate adds water (3000ml).Finish, insulation growing the grain.Suction filtration is dry obtains yellow solid object 105.
Comparative example 1
Adopt a kind of Simultaneously test pool horse degree amine of Chinese patent application publication No. CN 103645259A and the method for related substance thereof.
Test method: high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD)
Test condition:
Instrument: Agilent1260series high performance liquid chromatograph.
Chromatographic column: Agilent ZORBAX SB-C185 μm of 4.6 × 150mm.
Mobile phase: take pH value as the acetum of 2.6 ~ 3.0 be mobile phase A, take methyl alcohol as Mobile phase B, according to the form below carries out gradient elution.
Column temperature: 20 ~ 35 DEG C.
Flow velocity: be 0.5 ~ 1.2ml/min.
Determined wavelength: 226nm.
Specific experiment operates:
Need testing solution: precision takes pool horse degree amine 12.5mg, puts in 100ml measuring bottle, adds acetonitrile 20ml and make dissolving, add Mobile phase B and be diluted to scale, shake up, to obtain final product.See CN 103645259A instructions 5-6 page
Specificity solution: get pool horse degree amine need testing solution, add 5 known impurities in right amount: raw material 1:3-amino-2,6,-piperidine dione, intermediate: 3-aminophthalic acid, raw material 2:3-nitrophthalic acid, accessory substance 1:4 – nitro-2-(2,6-dioxo-piperidin-3-base)-isoindoline-1,3-diketone, accessory substance 2:5-amino-2-(2,6-dioxo-piperidin-3-base)-isoindoline-1,3-diketone.
The chromatographic peak retention time of known raw material, intermediate or accessory substance sees the following form:
Comparative example 2
Test method: high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD) test condition:
Chromatographic column: ACE C18 post 150 × 4.6mm, 3 μm
Mobile phase: take methyl alcohol as mobile phase A, with 25mM ammonium acetate (add formic acid and adjust pH=5.5), for Mobile phase B, according to the form below carries out gradient elution.
Flow velocity: 0.7ml/min
Column temperature: 30 DEG C
Test findings: pool horse degree amine main peak and five impurity peaks degree of separation are all less than 5, can only detect pool horse degree amine and two known impurities, and amino-2,6 piperidine diones of 3-do not retain, and 3-aminophthalic acid and 3-nitrophthalic acid degree of separation are less than 1.
Embodiment 1
Test method: high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD)
Test condition:
Mobile phase: with perfluorooctane sulfonate 1.08g, phosphoric acid 0.5ml, is diluted with water to 1000ml, regulates pH to 3.0-acetonitrile (volume ratio 90:10) to be mobile phase A with NaOH, with methanol-acetonitrile (volume ratio 50:50) for Mobile phase B, according to the form below carries out gradient elution.
UV-detector: determined wavelength 215nm
Column temperature: 25 DEG C
Chromatographic column: Inertsil ODS-3, packing material size 5 μm, long 25cm, internal diameter 4.6mm
Flow velocity: 1.0ml/min
Sampling volume: 20 μ l
Concrete test operation:
Get PMDA, CAV23-IMP01, CAV23-IMP02, CAV23-IMP03, CAV23-IMP04, CAV23-IMP05, CAV23-IMP06 are appropriate, dissolve with 40% acetonitrile solution and dilute respectively and make certain density solution, measure 20 μ l injection liquid chromatographies, record chromatogram; And horse degree amine aqueous solution and each dirt solution mixing sample introduction will be moored, record chromatogram, test findings sees the following form, and measurement result sees the following form.
The inventive method can effectively be separated PMDA, CAV23-IMP01, CAV23-IMP02, CAV23-IMP03, CAV23-IMP04, CAV23-IMP05, CAV23-IMP06.
Embodiment 2
Test method: high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD)
Test condition:
Mobile phase: with perfluorooctane sulfonate 1.08g, phosphoric acid 0.5ml, is diluted with water to 1000ml, regulates pH to 3.0-acetonitrile (volume ratio 90:10) to be mobile phase A with NaOH, with methanol-acetonitrile (volume ratio 50:50) for Mobile phase B, according to the form below carries out gradient elution.
UV-detector: determined wavelength 215nm
Column temperature: 25 DEG C
Chromatographic column: Luna 5u C18100A post, 4.6 × 250mm, 5um
Flow velocity: 1.0ml/min
Sampling volume: 20 μ l
Concrete test operation:
Get PMDA, CAV23-IMP01, CAV23-IMP02, CAV23-IMP03, CAV23-IMP04, CAV23-IMP05, CAV23-IMP06 are appropriate, dissolve with 40 volume ratio % acetonitrile solutions and dilute respectively and make certain density solution, measure 20 μ l injection liquid chromatographies, record chromatogram; And horse degree amine aqueous solution and each dirt solution mixing sample introduction will be moored, record chromatogram, test findings sees the following form, and measurement result sees the following form.
Embodiment 3
Test method: high performance liquid chromatography (Chinese Pharmacopoeia 2010 editions two annex VD)
Test condition:
Mobile phase: with perfluorooctane sulfonate 1.08g, phosphoric acid 0.5ml, is diluted with water to 1000ml, regulates pH to 3.0-acetonitrile (volume ratio 90:10) to be mobile phase A with NaOH, with methanol-acetonitrile (volume ratio 50:50) for Mobile phase B, carry out gradient elution.
Determined wavelength: 215nm
Flow velocity: 1.0ml/min
Column temperature: 25 DEG C
Sampling volume: 20 μ l
Chromatographic column: Inertsil ODS-3V post, 4.6 × 250mm, 5um
Concrete test operation:
The preparation of system suitability solution: precision takes PMDA, CAV23-IMP01, CAV23-IMP02, CAV23-IMP03, CAV23-IMP04, CAV23-IMP05, CAV23-IMP06 is appropriate, and solubilizer dissolves and dilutes to be made about containing PMDA 0.2mg/ml, about containing CAV23-IMP01, CAV23-IMP02, CAV23-IMP03, CAV23-IMP04, CAV23-IMP05, the solution of CAV23-IMP06 each impurity 0.2 μ g/ml, as system suitability solution.
System suitability: get system suitability solution 20 μ l injection liquid chromatography, between PMDA and each impurity, degree of separation should conform with the regulations, and each impurity can detect, theoretical cam curve is pressed PMDA and is calculated, and should be not less than 3000; The tailing factor of PMDA must not be greater than 2.0 (typical chromatogram is shown in accompanying drawing 1).
Impurity contrast solution: precision takes CAV23-IMP01, CAV23-IMP02, CAV23-IMP03, CAV23-IMP04, CAV23-IMP05, CAV23-IMP06 are appropriate, and solubilizer dissolves and dilutes the solution (typical chromatogram is shown in accompanying drawing 2) made about containing 0.2 μ g in every 1ml.
Need testing solution: it is appropriate that precision takes pool horse degree amine capsule 's content, and solubilizer is appropriate, ultrasonic 20min, constant volume, make the solution about containing PMDA 0.2mg in every 1ml, filter, get subsequent filtrate in right amount as need testing solution (typical chromatogram is shown in accompanying drawing 3).
Contrast solution: precision measures 1ml need testing solution, puts in 100ml measuring bottle, with solvent dilution to scale, shakes up, in contrast solution.
Get reference substance solution 20 μ l injection liquid chromatography, conditioning instrumentation sensitivity, makes the peak height of PMDA chromatographic peak be about 10 ~ 25% of full scale.Precision measures impurity contrast solution, need testing solution and each 20 μ l of contrast solution, respectively injection liquid chromatography, and record chromatogram is to 50min.
Claims (10)
1. moor a high-efficiency liquid chromatography method for detecting for horse degree amine or its oral solid formulation, this detection method comprises the steps:
(1) compounding system adaptability solution;
(2) system suitability test is carried out;
(3) test solution is prepared;
(4) measure according to following high-efficient liquid phase chromatogram condition:
Mobile phase: with ion pair phosphate buffer-acetonitrile for mobile phase A take methanol-acetonitrile as Mobile phase B;
UV-detector: determined wavelength is 200 ~ 400nm;
Chromatographic column: take octadecylsilane chemically bonded silica as filling agent;
Flow velocity: 0.5 ~ 2.0ml/;
Column temperature: 10 ~ 60 DEG C.
2. detection method according to claim 1, wherein, described UV-detector: determined wavelength is 200 ~ 240nm, is more preferably 215nm; Or
Described chromatographic column: take octadecylsilane chemically bonded silica as filling agent, theoretical cam curve calculates by pool horse degree amine, is not less than 2000, is preferably not less than 5000; The tailing factor of pool horse degree amine is less than 2.0; Or
Described flow velocity: be 1.0ml/min; Or
Described column temperature: be 20 ~ 40 DEG C more preferably, is 25 DEG C.
3. detection method according to claim 1, wherein, described ion pair is alkyl sodium sulfonate, preferably, is perfluorooctane sulfonate.
4. detection method according to any one of claim 1 to 3, wherein, the pH of ion pair phosphate buffer is 2.0-8.0, preferably 3.0.
5. detection method according to claim 4, wherein, mobile phase A, the volume ratio of described ion pair phosphate buffer and acetonitrile is 0-100:100-0; Mobile phase B, the volume ratio of described methyl alcohol and acetonitrile is 0-100:100-0.
6. detection method according to claim 5, wherein, mobile phase A is with perfluorooctane sulfonate 1.08g, and phosphoric acid 0.5ml, is diluted with water to 1000ml, and regulate pH to 3.0-acetonitrile with NaOH, volume ratio is 90:10; Mobile phase B is the methanol-acetonitrile of volume ratio 50:50.
7. detection method according to claim 1, wherein, the preparation of described system suitability solution refers to that precision takes pool horse degree amine, pool horse degree amine impurity, add 40 volume % acetonitrile solutions to dissolve and dilute and make about containing pool horse degree amine 0.2mg/ml, about containing the solution of pool horse degree amine impurity 0.2 μ g/ml, as system suitability solution.
8. detection method according to claim 1, wherein, described system suitability refers to gets system suitability solution 20 μ l injection liquid chromatography, between pool horse degree amine and its each impurity, degree of separation should conform with the regulations, each impurity can detect, theoretical cam curve calculates by pool horse degree amine, should be not less than 3000; The tailing factor of pool horse degree amine must not be greater than 2.0.
9. detection method according to claim 1, wherein, carries out gradient elution with mobile phase A and Mobile phase B.
10. detection method according to claim 9, wherein, described gradient is
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510182078.4A CN104749289A (en) | 2015-04-16 | 2015-04-16 | Method for detecting and separating pomalidomide related substances by use of high performance liquid chromatography |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510182078.4A CN104749289A (en) | 2015-04-16 | 2015-04-16 | Method for detecting and separating pomalidomide related substances by use of high performance liquid chromatography |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104749289A true CN104749289A (en) | 2015-07-01 |
Family
ID=53589283
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510182078.4A Pending CN104749289A (en) | 2015-04-16 | 2015-04-16 | Method for detecting and separating pomalidomide related substances by use of high performance liquid chromatography |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104749289A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021194253A1 (en) * | 2020-03-25 | 2021-09-30 | 주식회사 삼양홀딩스 | Oral tablet composition of pomalidomide and method for preparing same |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103645259A (en) * | 2013-12-12 | 2014-03-19 | 深圳海王药业有限公司 | Method for simultaneously determining 4-amino-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione and related substances thereof |
| CN105588902A (en) * | 2014-11-12 | 2016-05-18 | 南京卡文迪许生物工程技术有限公司 | Method of detecting and separating related substances in pomalidomide through high performance liquid chromatography |
-
2015
- 2015-04-16 CN CN201510182078.4A patent/CN104749289A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103645259A (en) * | 2013-12-12 | 2014-03-19 | 深圳海王药业有限公司 | Method for simultaneously determining 4-amino-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione and related substances thereof |
| CN105588902A (en) * | 2014-11-12 | 2016-05-18 | 南京卡文迪许生物工程技术有限公司 | Method of detecting and separating related substances in pomalidomide through high performance liquid chromatography |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021194253A1 (en) * | 2020-03-25 | 2021-09-30 | 주식회사 삼양홀딩스 | Oral tablet composition of pomalidomide and method for preparing same |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2017152689A1 (en) | High-sensitivity analysis method for imatinib genotoxic impurities | |
| CN105588886B (en) | method for determining impurities in apremilast and its preparation by liquid chromatography | |
| CN110133149B (en) | Method for separating and measuring LCZ696 and impurities thereof | |
| CN104965041A (en) | High performance liquid chromatography detection method for parecoxib sodium isomer | |
| CN102375033B (en) | High performance liquid chromatographic analysis method of bendamustine hydrochloride and its related substances | |
| CN105467021B (en) | A kind of method in relation to substance in HPLC method separation determination paricalcitol bulk pharmaceutical chemicals and preparation | |
| CN103076421B (en) | Analytic method for related substance examination of rebamipide | |
| CN105588902A (en) | Method of detecting and separating related substances in pomalidomide through high performance liquid chromatography | |
| CN101929985A (en) | Method for measuring atorvastatin calcium associated matters by high performance liquid chromatography | |
| CN109490444B (en) | Method for separating and measuring degradation impurities in dutasteride raw material medicine and preparation by HPLC (high performance liquid chromatography) method | |
| CN111024831A (en) | Method for separating moxifloxacin hydrochloride and impurities thereof by high performance liquid chromatography | |
| CN104749289A (en) | Method for detecting and separating pomalidomide related substances by use of high performance liquid chromatography | |
| CN108680678A (en) | Measure methods of the song Ge Lieting in relation to substance | |
| CN104764840B (en) | The separation of palonosetron Hcl and impurity and detection method | |
| CN106706769B (en) | Separation and determination method of empagliflozin and optical isomer thereof | |
| CN107525877B (en) | Method for separating and determining brexpiprazole and impurities thereof by adopting liquid chromatography | |
| CN107228909B (en) | Method for measuring acotiamide hydrochloride raw material medicine and related substances in preparation thereof by using HPLC | |
| CN106290695B (en) | Method for separating and measuring desonide and related impurities | |
| CN101929988B (en) | Method for detecting febuxostat-associated matters by using high performance liquid chromatography | |
| CN103645259B (en) | Method for simultaneously determining 4-amino-2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione and related substances thereof | |
| CN110554102A (en) | Detection method of sugammadex sodium | |
| CN114814060B (en) | Detection method of valsartan amlodipine tablet related substances | |
| Wang et al. | Detection of two genotoxic impurities in drug substance and preparation of imatinib mesylate by LC–MS/MS | |
| CN104730194A (en) | Bilastine detection method | |
| CN106153756B (en) | High performance liquid chromatography for detecting rapamycin in everolimus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150701 |