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Date Published: 25/12/2023
Online Published: 25/12/2023
Abstract Views: 73
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DOI: https://doi.org/10.58490/ctump.2023i69.976
Issue
No. 69 (2023)
Section
Article
How to Cite
Lu , T. P., Tran, H. T. C., Nguyen , U. K., Ta , T. T., Kim , T. T. T., Tran, V. H., & Truong , N. T. (2023). DEVELOPMENT AND VALIDATION OF LC-MS/MS FOR ANALYZING POTENTIAL GENOTOXIC IMPURITY ETHYL-(E/Z)-3-(2- CARBETHOXY-2-CYANOETHENYL) AMINO-1H-PYRAZOL-4- CARBOXYLAT IN ALLOPURINOL. Cantho Journal of Medicine and Pharmacy, 69, 164-171. https://doi.org/10.58490/ctump.2023i69.976

DEVELOPMENT AND VALIDATION OF LC-MS/MS FOR ANALYZING POTENTIAL GENOTOXIC IMPURITY ETHYL-(E/Z)-3-(2- CARBETHOXY-2-CYANOETHENYL) AMINO-1H-PYRAZOL-4- CARBOXYLAT IN ALLOPURINOL

Thien Phuc Lu 1,, Ha Thai Chau Tran1, Uy Khang Nguyen 1, Trung Tin Ta 1, Thi Thu Trinh Kim 1, Viet Hung Tran2, Ngoc Tuyen Truong 3
1 Can Tho University of Medicine and Pharmacy
2 Institute of Drug Quality Control Ho Chi Minh City
3 University of Medicine and Pharmacy at Ho Chi Minh City

Main Article Content

Abstract

Background: ICH M7(R1) Guideline on the limits of potentially toxic or mutagenic impurities requires rigorous testing against Pharmacopoeia because of their impact on clinical efficacy and patient safety. Therefore, check the quality of raw materials as well as finished drug products, especially drugs on the 7th current list of essential drugs of Vietnam such as allopurinol and related impurities F by highly sensitive technique LC-MS/MS trend and urgency.  Objectives: To develop and validate a process for quantification of impurity ethyl-(E/Z)-3-(2-carbethoxy-2cyanoethenyl) amino-1H-pyrazol-4-carboxylat (F impurity according to USP standard 2023) of allopurinol according to the guidelines of ICH M7 (R1) in genotoxic impurities by high-performance liquid chromatography twice mass spectrometry. Materials and methods: Related to impurity F of allopurinol, develop, and validate the quantitative procedure by LC-MS/MS according to ICH Q2(R2); ICH M7(R1) and EC-657/2002 guidelines. Results: Chromatographic conditions: Phenomenex Gemini NX C18 (150 mm x 4.6 x 5 µm) kept at 25°C, mobile phase acetonitrile - formic acid water 0.05% (85:15) according to isocratic program, sample injection volume 10 µL, flow rate


0,8 mL/min.  The analyte is detected by an MS/MS detector, mass spectrometry fractions→ quantitative fragmentation 279.10→233.00. Process validation according to ICH and EC-657/2002 guidelines: procedure achieves specificity – selectivity; the calibration curves were linear over the range of 3 - 100 ppb and the correlation coefficient is 0,997; low detection limit from 1 to 3 ppb; quantitative limit: 3 ppb; accuracy achieved recovery rate from 99.30 – 101.37%, precision meets the requirements RSD < 2%. Conclusion: The process of quantification of Ethyl-(E/Z)-3-(2carbethoxy-2-cyanoethenyl) amino-1H-pyrazol-4-carboxylat impurities of allopurinol has been developed and validated by LC-MS/MS method.

Article Details

Keywords

Ethyl-(E/Z)- 3-(2-carbethoxy-2-cyanoethyl) amino-1H-pyrazol-4-carboxylat impurity, ICH M7(R1), genotoxic impurity

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