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Method for detecting afatinib-dimaleate-related substances through high performance liquid chromatography

A high-performance liquid chromatography and afatinib maleate technology, which is applied in the field of high-performance liquid chromatography for detecting afatinib maleate related substances, can solve the problem that the product quality cannot be effectively controlled, and the process impurity degradation cannot be completely separated. problem, to achieve the effect of good accuracy, high sensitivity and strong specificity

Active Publication Date: 2016-05-18
BEIJING COLLAB PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] At present, in the existing detection methods, there is no HPLC detection method for the above 13 related substances at the same time. Only an article "HPLC method for the determination of alfatinib" was published in the Journal of Pharmaceutical Research, Volume 33, No. 6, 2014. The content of Afatinib Tablets” document, the method described in this document is used for the determination of the content of Afatinib Tablets, and its specificity inspection item only verifies that the blank excipients have no interference with the determination of Afatinib, and this method cannot achieve all The complete separation of process impurities and degraded impurities cannot effectively control product quality

Method used

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  • Method for detecting afatinib-dimaleate-related substances through high performance liquid chromatography
  • Method for detecting afatinib-dimaleate-related substances through high performance liquid chromatography
  • Method for detecting afatinib-dimaleate-related substances through high performance liquid chromatography

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: System suitability testing

[0044] Instrument: Shimadzu LC-20A high performance liquid chromatograph and its workstation VWD (or PDA) detector;

[0045] Chromatographic column: WatersXBridgeC184.6×250mm, 3.5μm;

[0046] Mobile phase A: 0.002mol / L dipotassium hydrogen phosphate buffer (use 2mol / L sodium hydroxide to adjust the pH to 10.0);

[0047] Mobile phase B: acetonitrile;

[0048] Detection wavelength: 254nm;

[0049] Flow rate: 0.5mL / min;

[0050] Injection volume: 10μL;

[0051] Column temperature: 40°C;

[0052] Gradient elution table: see Table 1;

[0053] Diluent: Methanol;

[0054] Take an appropriate amount of afatinib maleate (approximately equivalent to 25mg of afatinib), put it in a 50ml measuring bottle, measure the appropriate amount of impurity I, SM1, CL-SM1, M, D stock solution, dissolve and dilute with methanol Made to contain maleic acid, afatinib, impurities I, SM1, CL-SM1, M, and D at concentrations of 0.24mg / ml, 0.5mg / ml, 5ug...

Embodiment 2

[0057] Example 2: Detection of afatinib and its impurity mixed solution

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

[0059] Chromatographic column: WatersXBridgeC184.6×250mm, 3.5μm;

[0060] Mobile phase A: 0.002mol / L dipotassium hydrogen phosphate buffer (use 2mol / L sodium hydroxide to adjust the pH to 10.0);

[0061] Mobile phase B: acetonitrile;

[0062] Detection wavelength: 254nm;

[0063] Flow rate: 0.5mL / min;

[0064] Injection volume: 10μL;

[0065] Column temperature: 40°C;

[0066] Gradient elution table: see Table 1;

[0067] Diluent: Methanol;

[0068] Measure the appropriate amount of afatinib maleate, impurity A, B, E, F, G, H, J, L, M, SM1, CL-SM1, and I stock solutions, dissolve and dilute with methanol to make A mixed solution of about 2.5ug / ml of Fatinib, about 5ug / ml of impurity I, and about 0.75ug / ml of other impurity monomers is used as a mixed solution of Afatinib and its im...

Embodiment 3

[0078] Embodiment 3: detection of afatinib bulk drug

[0079] Instrument: Shimadzu LC-20A high performance liquid chromatograph and its workstation VWD (or PDA) detector;

[0080] Chromatographic column: WatersXBridgeC184.6×250mm, 3.5μm;

[0081] Mobile phase A: 0.002mol / L dipotassium hydrogen phosphate buffer (use 2mol / L sodium hydroxide to adjust the pH to 10.0);

[0082] Mobile phase B: acetonitrile;

[0083] Detection wavelength: 254nm;

[0084] Flow rate: 0.5mL / min;

[0085] Injection volume: 10μL;

[0086] Column temperature: 40°C;

[0087] Gradient elution table: see Table 1;

[0088] Diluent: Methanol;

[0089] Take afatinib maleate, add diluent to make a solution containing about 0.5 mg / mL of afatinib.

[0090] Get the maleic acid afatinib solution, measure according to the chromatographic conditions of this embodiment, record the chromatogram, the results are shown in Figure 4 .

[0091] Figure 4 The chromatographic peak whose retention time is 47.635min...

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Abstract

The invention relates to the technical field of analytical chemistry and discloses a method for detecting afatinib-dimaleate-related substances through high performance liquid chromatography. According to the method, an afatinib dimaleate raw material drug or preparation is prepared into a detection solution with diluents, octadecyl silane keys and silica gel serve as fixing phases, inorganic salt buffer liquid is adopted as a flowing phase A, an organic phase serves as a flowing phase B, gradient elution is conducted, and an HPLC spectrogram is recorded under afatinib absorption wave length. According to the method, a chromatographic column with the octadecyl silane keys and silica gel serving as filler is adopted, the inorganic salt buffering liquid-organic phase for regulating the proper pH value serves as the flowing phase, the contents of related substances existing possibly of the afatinib dimaleate and a preparation thereof can be measured quantitatively, main impurities and various impurities can be completely separated, the peak pattern is good, regulations of Chinese pharmacopoeia are satisfied, the quality of the afatinib dimaleate and a preparation product containing the afatinib dimaleate is effectively controlled, and the method is high 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 related substances of afatinib maleate 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 is 850140-73-7; the m...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/60
CPCG01N30/02G01N30/60G01N2030/027
Inventor 姚华张雪男邹德超张秋佳赵大龙王珂
Owner BEIJING COLLAB PHARMA
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