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Sci. Pharm. 2015, 83(2), 269-278; doi:10.3797/scipharm.1502-05

A Validated HPLC/MS Limit Test Method for a Potential Genotoxic Impurity in Cilostazol and its Quantification in the API and in the Commercially Available Drug Product

R&D Department, Dipharma Francis srl, Via Bissone 5, Baranzate (MI), Italy.
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Received: 19 February 2015 / Accepted: 26 March 2015 / Published: 26 March 2015
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Abstract

Cilostazol is a selective inhibitor of type 3 phosphodiesterase. 5-(3-Chloro-propyl)-1-cyclohexyl-1H-tetrazole, used as an intermediate in the synthesis of cilostazol, has a primary alkyl chloride group, a well-known alerting function for genotoxic activity. Upon request from a regulatory agency, a limit test in accordance with ICH Q2(R1) added with the accuracy of a recovery test of 5-(4-chlorobutyl)-1-cyclohexyl-1H-tetrazole in cilostazol was developed and validated. The application of the method highlighted the need to optimize the purification process to ensure levels of this potential genotoxic impurity in the final active pharmaceutical ingredient below the established limit. Also, the analytical method was suitable to determine the amount of the impurity in samples of the commercially available drug product, which showed the levels to be above the established threshold of toxicological concern (TTC).
Keywords: Cilostazol; Potential genotoxic impurity; HPLC/MS; Limit test method; Validation Cilostazol; Potential genotoxic impurity; HPLC/MS; Limit test method; Validation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

BRAY, L.; MONZANI, L.; BRUNOLDI, E.; ALLEGRINI, P. A Validated HPLC/MS Limit Test Method for a Potential Genotoxic Impurity in Cilostazol and its Quantification in the API and in the Commercially Available Drug Product. Sci. Pharm. 2015, 83, 269-278.

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