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. 2025 Sep;39(9):e70189.
doi: 10.1002/bmc.70189.

Development of an Efficient Method to Quantitatively Estimate Dichloroacetic Acid Genotoxic Impurity in Cetirizine Dihydrochloride by Liquid Chromatography-Mass Spectrophotometry

Mithun M Gharat  1 , Pallavi T Roy  1 , Amit N Gosar  2 , Tabrez A Shaikh  2 , Gurumeet C Wadhava  3 , Nitin A Mirgane  1
Affiliations

Development of an Efficient Method to Quantitatively Estimate Dichloroacetic Acid Genotoxic Impurity in Cetirizine Dihydrochloride by Liquid Chromatography-Mass Spectrophotometry

Mithun M Gharat et al. Biomed Chromatogr. 2025 Sep.

Abstract

An LC-MS (liquid chromatography-mass spectrometry) methodology is developed for the precise analysis of dichloroacetic acid (DCAA) genotoxic impurity with high sensitivity and selectivity in a Cetirizine dihydrochloride (CTZ) drug substance. In accordance with the "threshold of toxicological concern (TTC)," the carryover of DCAA in a CTZ is done at a limit of 25 ppm in the sample. The present methodology is validated as per "International Council for Harmonization (ICH)" guidelines, and the detection limit and the quantitation limit are 0.4 and 1.2 ppm, respectively. The linearity study was conducted, and the coefficient of regression was found to be 0.9946. The method's accuracy was confirmed by the finding the percentage of recovered spiked DCAA in the drug, which ranged from 93.47% to 99.80%. Results indicated that the methodology was reliable, precise, and reproducible. The method can be extended for the determination of DCAA genotoxic impurity in a CTZ drug substance (API) samples by LC-MS.

Keywords: Cetirizine dihydrochloride (CTZ); dichloroacetic aicd (DCAA); genotoxic impurity; liquid chromatography–mass spectrophotometer; validation.

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