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Volume 83
Issue 2
10.3797/scipharm.1502-05
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Scientia Pharmaceutica is published by MDPI from Volume 84 Issue 3 (2016). Previous articles were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence, and they are hosted by MDPI on mdpi.com as a courtesy and upon agreement with Austrian Pharmaceutical Society (Österreichische Pharmazeutische Gesellschaft, ÖPhG).
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Article

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

by
Luigi BRAY
,
Luca MONZANI
,
Enrico BRUNOLDI
* and
Pietro ALLEGRINI
R&D Department, Dipharma Francis srl, Via Bissone 5, Baranzate (MI), Italy.
*
Author to whom correspondence should be addressed.
Sci. Pharm. 2015, 83(2), 269-278; https://doi.org/10.3797/scipharm.1502-05
Submission received: 19 February 2015 / Accepted: 26 March 2015 / Published: 26 March 2015
Versions Notes

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

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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. https://doi.org/10.3797/scipharm.1502-05

AMA 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. Scientia Pharmaceutica. 2015; 83(2):269-278. https://doi.org/10.3797/scipharm.1502-05

Chicago/Turabian Style

BRAY, Luigi, Luca MONZANI, Enrico BRUNOLDI, and Pietro ALLEGRINI. 2015. "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" Scientia Pharmaceutica 83, no. 2: 269-278. https://doi.org/10.3797/scipharm.1502-05

APA Style

BRAY, L., MONZANI, L., BRUNOLDI, E., & ALLEGRINI, P. (2015). 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. Scientia Pharmaceutica, 83(2), 269-278. https://doi.org/10.3797/scipharm.1502-05

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