Method for detecting afatinib dimaleate isomers and main degradation impurities through high performance liquid chromatography

A technology of high-performance liquid chromatography and maleic acid alpha, which is applied in the direction of measuring devices, instruments, scientific instruments, etc., can solve problems such as poor accuracy, poor specificity, and complicated operation, and achieve good accuracy, strong specificity, and sensitivity high effect

Active Publication Date: 2016-06-29
BEIJING COLLAB PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the operation method is relatively complicated, and the cis-isomer of afatinib, the impurity I and the enantiomer of afatinib (Table 1) cannot be effectively separated. The method has poor specificity, complicated operation and poor accuracy. , there is a certain risk to the quality control of the product

Method used

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  • Method for detecting afatinib dimaleate isomers and main degradation impurities through high performance liquid chromatography
  • Method for detecting afatinib dimaleate isomers and main degradation impurities through high performance liquid chromatography
  • Method for detecting afatinib dimaleate isomers and main degradation impurities through high performance liquid chromatography

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1: The HPLC detection of the mixed solution of Afatinib maleate and its isomers

[0034] Instrument: Shimadzu LC-20A high performance liquid chromatograph and its workstation VWD (or PDA) detector;

[0035] Column: ID, 4.6×250mm, 5μm;

[0036] Mobile phase: n-hexane-ethanol-diethylamine (volume ratio 80:20:0.1)

[0037] Detection wavelength: 253nm;

[0038] Flow rate: 0.8mL / min;

[0039] Injection volume: 10μL;

[0040] Column temperature: 30°C;

[0041] Diluent: absolute ethanol;

[0042] Take afatinib maleate, impurity D (cis-isomer of afatinib), impurity I and afatinib enantiomer (AFTN-R), dissolve and dilute with absolute ethanol to prepare A mixed solution containing 0.5 mg / ml of afatinib, 2 μg / ml of impurity D, 0.5 μg / ml of impurity I and 0.5 μg / ml of AFTN-R was formed.

[0043] Take blank solvent (diluent) and mixed solution respectively, measure according to the above-mentioned chromatographic conditions, record the chromatogram, the results ...

Embodiment 2

[0045] Embodiment 2: detection of afatinib bulk drug

[0046] Instrument: Shimadzu LC-20A high performance liquid chromatograph and its workstation VWD (or PDA) detector;

[0047] Column: ID, 4.6×250mm, 5μm;

[0048] Mobile phase: n-hexane-ethanol-ethylenediamine (volume ratio 79:21:0.15)

[0049] Detection wavelength: 253nm;

[0050] Flow rate: 0.8mL / min;

[0051] Injection volume: 10μL;

[0052] Column temperature: 30°C;

[0053] Diluent: absolute ethanol;

[0054] Take an appropriate amount of afatinib maleate raw material, dissolve and dilute with absolute ethanol to prepare a solution containing 0.5 mg / ml of afatinib.

[0055] Get maleic acid afatinib solution, measure according to the above-mentioned chromatographic conditions, record the chromatogram, the results are shown in image 3 .

[0056] image 3 The chromatographic peak whose retention time is 19.725min is the afatinib chromatographic peak. As can be seen from the figure, the optical purity of afatin...

Embodiment 3

[0057] Example 3: Detection of afatinib preparations

[0058] Instrument: Shimadzu LC-20A high performance liquid chromatograph and its workstation VWD (or PDA) detector;

[0059] Column: ID, 4.6×250mm, 5μm;

[0060] Mobile phase: n-hexane-ethanol-triethylamine (volume ratio 81:19:0.05)

[0061] Detection wavelength: 253nm;

[0062] Flow rate: 0.8mL / min;

[0063] Injection volume: 10μL;

[0064] Column temperature: 30°C;

[0065] Diluent: absolute ethanol;

[0066] Take an appropriate amount of fine powder of afatinib maleate preparation, approximately equivalent to 25mg of afatinib, put it in a 50mL measuring bottle, add an appropriate amount of diluent and sonicate for 10min, add diluent to make up to the mark, shake well, filter, Take the continued filtrate as the test solution. Prepare the blank excipient solution in the same way.

[0067] Take blank auxiliary material solution and need testing solution respectively, measure according to above-mentioned chromatog...

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Abstract

The invention relates to the technical field of analytical chemistry and discloses a method for detecting afatinib dimaleate isomer and main degradation impurities through a high performance liquid chromatography.According to the method, afatinib dimaleate raw materials or preparations are compounded into a detection solution with diluent, bonding amylose-trichlorobenzene carbamic acid ester serves as a stationary phase, a normal hexane-ethanol-organic base solution serves as a mobile phase for isocratic elution, and an HPLC spectrogram is recorded under afatinib absorption wavelength.According to the method, a chromatographic column with trichlorobenzene carbamic acid ester serving as a filling material, the normal hexane-ethanol-organic base solution serves as the mobile phase, the content of isomers existing in afatinib dimaleate and preparations thereof can be measured quantitatively, afatinib, the isomers and the main impurities can be separated completely, the peak pattern is good, the method meets the specifications in Chinese Pharmacopoeia, quality of afatinib dimaleate and afatinib dimaleate preparation products is effectively controlled, and the method is great in specificity, high in sensitivity and good in accuracy.

Description

technical field [0001] The invention relates to the technical field of analytical chemistry, in particular to a method for detecting maleic acid afatinib isomers and mainly degrading impurities by using high performance liquid chromatography. Background technique [0002] Afatinib maleate is an irreversible ErbB family blocker, which can selectively and effectively block the signal transduction of ErbB family receptors (EGFR, HER2 [ErbB2] and ErbB4) and block the relationship between cancer cell growth and Split related main channels. For the first-line treatment of advanced non-small cell lung cancer (NSCLC) and HER2-positive advanced breast cancer patients (for the treatment of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations). [0003] Afatinib maleate chemical name: 4-Dimethylamino-but-2(E)-enoic acid [4-(3-chloro-4-fluoroanilino)-7-(tetrahydrofuran-3(S)- Oxy)-quinazolin-6-yl]amide, di-2(Z)-butenedioate. The CAS number...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
CPCG01N30/02G01N2030/027
Inventor 姚华张秋佳邹德超赵大龙王珂
Owner BEIJING COLLAB PHARMA
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