Document Type: Original Article

Authors

Micro Labs Ltd., API R&D Centre, Bommasandra Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore-560105, Karnataka, India.

Abstract

A new LC-MS based method was developed to detect three potential genotoxic impurities namely, N',N'''-(4,6-dichloropyrimidine-2,5-diyl)bis[N,N-dimethyl(imidoformamide)]} (Impurity-I), {N-(2-amino-4-chloro-6-{[(1S,2R)-2-(hydroxymethyl)cyclopent-3-en-1-yl]amino}pyrimidin-5-yl)formamide} (Impurity-II) and {(1R,5S)-5-[(2,5-diamino-6-chloropyrimidin-4-yl)amino]cyclopent-2-en-1-yl}methanol (Impurity-III), at low level in Abacavir sulfate, a nucleoside reverse transcriptase inhibitor. It utilizes Zorbax phenyl hexyl column (150 mm x 4.6 mm, 3.5 μm) with electrospray ionization in selected ion monitoring (SIM) mode for quantitation of these PGIs. The method is able to quantify Impurity-I at 0.74 ppm, Impurity-II and Impurity-III at 0.73 ppm with respect to 5.0 mg/mL of Abacavir sulfate. The method was found to be linear in the range of LOQ to 150% of Toxicological Threshold Concentration level of 2.5 ppm. The correlation coefficients of PGI’s obtained were >0.999 in each case. The method accuracy of these PGI’s is in the range between 88.7-115.0%. The method is sensitive, specific, linear, accurate, precise and meets the criteria of validation as per International Conference on Harmonization.

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