A method for detecting 1-(2-hydroxyethyl)piperazine in dasatinib

A technology of dasatinib and hydroxyethyl, applied in the field of drug analysis, achieves high precision, simple operation and good stability

Active Publication Date: 2019-01-29
珠海润都制药股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no detection method of 1-(2-hydroxyethyl)piperazine impurity in bibliographical reports in dasatinib, and the present invention proposes a kind of 1-(2-hydroxyethyl)piperazine in dasatinib for the first time The detection method of oxine impurities, which uses the chiral derivatization reagent N-A-(5-fluoro-2,4-dinitrophenyl)-L-alaninamide (FDAA) for pre-column derivatization, and realizes the use of ordinary C18 chromatography Separation and determination of 1-(2-hydroxyethyl)piperazine impurity in dasatinib by column

Method used

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  • A method for detecting 1-(2-hydroxyethyl)piperazine in dasatinib
  • A method for detecting 1-(2-hydroxyethyl)piperazine in dasatinib
  • A method for detecting 1-(2-hydroxyethyl)piperazine in dasatinib

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] (1) Experimental materials and instrument conditions

[0053] Instrument: HPLC: Agilent 1260; Column: Thermo Acclaim TM C18, 5μm, 4.6×250 mm; flow rate: 1.0mL / min; column temperature: 30℃; injection volume: 20μl; running time: 25min; detection wavelength: 340nm. Inject the blank solution, the reference substance solution and the test solution into the liquid chromatograph respectively, record the chromatogram, and the chromatographic conditions are as follows: Chromatographic column: use octadecylsilane bonded silica gel as filler; Temperature: 30°C; Injection volume: 20μl; Running time: 25min; Detection wavelength: 340nm; Mobile phase: 0.5%wt triethylamine (adjust pH to 3 with phosphoric acid)-acetonitrile, carry out gradient elution, the gradient is as shown in the table 1.

[0054] Table 1 - Gradient Elution Conditions

[0055] time (min)

mobile phase A

mobile phase B

0

75

25

15

25

75

16

75

25

25

75

...

Embodiment 2

[0068] Embodiment 2 detection method system applicability test of the present invention

[0069] The system suitability is realized by measuring the RSD of the peak area of ​​1-(2-hydroxyethyl)piperazine in the reference solution for 5 points, and it is required that the peak area of ​​1-(2-hydroxyethyl)piperazine in the reference solution is 5 points RSD≤2.0%. Prepare blank solution and reference substance solution as described in Example 1, under the chromatographic conditions described in Example 1, enter 1 needle of blank solution, 5 needles of reference substance solution, obtain the chromatogram, as figure 1 , figure 2 , image 3 and Figure 4 , according to the formula conversion results are shown in the table below:

[0070] Table 2 - System Suitability Determination Results

[0071]

[0072] The conclusion is: the RSD of the peak area of ​​1-(2-hydroxyethyl)piperazine in the reference solution of 5 is 0.9%, which meets the requirement that the RSD in the prot...

Embodiment 3

[0073] Embodiment 3 Detection method specificity test of the present invention

[0074] The specificity of the method is achieved by studying peak identification and selectivity, requiring that the blank solvent does not interfere with the detection; dasatinib positioning solution has no interference with the detection; 1-(2-hydroxyethyl)piperazine in the selective solution The degree of separation from adjacent peaks is ≥1.5; in the selective solution, the recovery rate of 1-(2-hydroxyethyl)piperazine should be between 90.0% and 110.0%. Prepare blank solution, reference solution, 1-(2-hydroxyethyl)piperazine positioning solution, test solution, dasatinib positioning solution and selective solution as described in Example 1.

[0075] After the system is balanced, inject 1 needle of blank solution, 1 needle of 1-(2-hydroxyethyl)piperazine positioning solution, 1 needle of dasatinib positioning solution, and 3 needles of selective solution, and record the chromatogram, such as ...

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Abstract

The invention provides a detection method for 1-(2-hydroxyethyl) piperazine impurity of Dasatinib. A chiral derivatization agent N-A-(5-fluorine-2,4-dinitrophenyl)-L- Alaninamide is adopted to performpre-column derivatization on the 1-(2-hydroxyethyl) piperazine of the Dasatinib, the separation and determination of 1-(2-hydroxyethyl) piperazine impurity of the Dasatinib is performed by adopting an ordinary C18 chromatographic column, the system completely accords with the guidance principle of the Chinese pharmacopeia method verification of system applicability, specialization, precision, quantification limit, detection limit, linearity, scope, accuracy, wearing property and the like. The method is used for mass control of the Dasatinib bulk drug.

Description

technical field [0001] The invention relates to an HPLC method for determining 1-(2-hydroxyethyl)piperazine in dasatinib, belonging to the technical field of drug analysis. Background technique [0002] Dasatinib, chemical name: N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl] -2-Methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide (monohydrate), trade name SPRYCEL, is an oral tyrosine kinase inhibitor developed by Bristol-Myers Squibb. Dasatinib is a highly effective small molecule multi-targeted second-generation tyrosine kinase inhibitor targeting BCR-ABL. It was originally developed as an inhibitor of the Src kinase family (such as Fyn, Yes, Src, and Lyk), but it also inhibits BCR-ABL, Eph A2, platelet growth factor receptor, and c-Kit, and, It is able to bind to other tyrosine and serine, threonine kinases such as mitogen-activated protein kinases, receptor tyrosine kinases, discotic domain receptors, etc. Dasatinib can effectively inhibit the proli...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N30/02G01N30/06
CPCG01N30/02G01N30/06
Inventor 韦静谢金昌张寨花周建
Owner 珠海润都制药股份有限公司
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