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Date Published: 28/02/2023
Online Published: 28/02/2023
Abstract Views: 572
Views PDF: 588
DOI: https://doi.org/10.58490/ctump.2023i57.608
Issue
No. 57 (2023)
Section
Article
How to Cite
Lu, T. P., Nguyen, D. G. B., Vuong, V. H., Truong, L. M. T., Truong, N. T., Tran, V. H., & Nguyen, D. T. (2023). DEVELOPMENT AND VALIDATION OF LC-MS/MS FOR ANALYZING IMPURITIES A, B, C, D, E, F IN ALLOPURINOL. Cantho Journal of Medicine and Pharmacy, 57, 147-153. https://doi.org/10.58490/ctump.2023i57.608

DEVELOPMENT AND VALIDATION OF LC-MS/MS FOR ANALYZING IMPURITIES A, B, C, D, E, F IN ALLOPURINOL

Thien Phuc Lu1,, Duy Gia Bao Nguyen1, Vinh Hung Vuong1, Le Minh Thu Truong1, Ngoc Tuyen Truong2, Viet Hung Tran3, Duc Tuan Nguyen2
1 Can Tho University of Medicine and Pharmacy
2 University of Medicine and Pharmacy at Ho Chi Minh City
3 Institute of Drug Quality Control Ho Chi Minh city

Main Article Content

Abstract

Background: Currently, the quality control of raw materials as well as finished products of the essential drug allopurinol before and during the production, circulation and storage needs to be closely monitored according to the provisions of the Vietnam Pharmacopoeia V; BP 2021; USP 44, especially related impurities, directly affect the treatment effectiveness and safety of patients. Objectives: To develop and validate a process for simultaneous quantification of 6 impurities A, B, C, D, E, Ethyl-(E/Z)-3-(2-carbethoxy-2-cyanoethyl) amino pyrazol- 4-carboxylate (F impurity according to USP standard 2022) of allopurinol in the finished product by high performance liquid chromatography twice mass spectrometry. Materials and methods: Related impurities A, B, C, D, E, F of allopuirnol, quantitative procedure was developed by liquid chromatography coupled to mass spectrometry (LC-MS/MS) system according to the verification instructions. ICH Q2(R2) and EC-657/2002 procedure specification. Results: The suitable mass spectrometry fractions for quantitative fragmentation were impurity A (126.9¦109.9); B (155,1¦138); C (178.8¦78,9); D (155.86 ¦127.9); E (183.87¦109.9); F (279.1¦187) and allopuirnol (136.9¦109.9). Mass spectrometry conditions: Vaporization temperature (oC): 400oC, vaporization gas rate (l/h): 900 l/h, Cone potential (V): 15-26V, capillary potential (kV): 4kV , impact gas chamber energy (V): 12-25V. Chromatographic conditions: column Gemini – NX C18 (15cm; 4,6mm; 5m ;Phenomenex), mobile phase acetonitrile - formic acid water 0.05% according to gradient program, column temperature 25˚C, sample injection volume 10 µL , flow rate 0.8 mL/min. Process validation according to ICH guidelines: procedure achieves specificity – selectivity; linearity with correlation coefficient from 0.995 to 0.999; detection limit from 3-10ppb; quantitative limit 10ppb; Accuracy accuracy meets the requirements RSD ≤ 2%. Conclusion: A process to simultaneously quantify 6 impurities of allopurinol by LC-MS/MS method was developed according to the guidelines of ICH.

Article Details

Keywords

Impurities A, impurities B, impurities C, impurities D, impurities E, Ethyl-(E/Z)3-(2-carbethoxy-2-cyanoethyl) amino pyrazol-4-carboxylate impurities (impurities according to USP standard 2022), LC-MS/MS, allopurinol

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