A VALIDATED CHIRAL LC METHOD FOR THE ENANTIOMERIC SEPARATION OF TOPOTECAN HYDROCHLORIDE ON IMMOBILIZED AMYLOSE BASED STATIONARY PHASE

Abstract

Author(s): Vitthal Dhakane and Milind Ubale*

A simple, rapid, isocratic, normal phase chiral HPLC method was developed and validated for the enantiomeric separation of topotecan, (S)-10- [(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione monohydrochloride, an antineoplastic drug substance. The enantiomers of topotecan were resolved on a Chiralpak ADH(immobilized amylose based stationary phase) column using a mobile phase consisting of Methanol:acetonitrile:diethyl amine (70:30:0.2, v/v/v) at a flow rate of 1.0 mL min-1. The resolution between both enantiomers was greater than 2 in the optimized method. The developed method was extensively validated and proved to be robust, enantioselective, accurate, precise, and suitable for quantitative determination of (R)-enantiomer in bulk drug substance and product.