a simple and sensitive method for the ultra trace determination of potential genotoxic impurities in abacavir sulfate by lc-ms

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 sulphate as 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 contends.