Abstract

QUANTITATIVE DETERMINATION OF METHYL-4-CHLOROBUTYRATE IN NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS BY GCMS USING ELECTRON IONIZATION

Perla Ganesh*, Ch. B. V. Narasimha Raju, Suman Gundlapalli, Dharamasoth Rama Devi, K. Basavaiah*

ABSTRACT

The objective of the present study was to develop and validate a trace level of Methyl-4-chlorobutyrate (MCB) impurity in Nucleoside Reverse Transcriptase Inhibitor (NRTI) drugs by using Gas Chromatography with Mass Spectroscopic method. A capillary Gas Chromatography (GC) column was used with a stationary phase 100% Dimethyl polysiloxane and the mode opted for Selective Ion Monitoring (SIM) comprised of an Electron Impact (EI) source. Methanol was used as a diluent and a dissolve-and-injection approach was adopted for sample introduction in a split mode. The calibration curves showed good linearity over the concentration range (Limit Of Quantitation (LOQ) to 150%) of 1.0 to 3.75 ppm. The correlation coefficient obtained was >0.99. The Limit Of Detection (LOD)achieved was about 0.3 ppm and the LOQ was 1.0 ppm. We strongly demonstrated the absence of matrix effect based on attained recovery of 94.4% at LOQ level, 93.2% at 50% of the SL, 106.34% at SL and 89.86% at 150% of the SL. A method was developed to trace the level of MCB impurity in NRTI drugs which fulfilled the analytical validation criteria from ppm level. Herein, we report the first validated method for MCB impurity in NRIT drugs.

Keywords: Low level determination, Gas chromatography-mass spectrometry, Nucleoside Reverse Transcriptase Inhibitor drug, Methyl-4-chlorobutyrate impurity.