ACTIVE-DRUG SUBSTANCE IMPURITY PROFILING - PART-II - LC MS/MS FINGERPRINTING/

Drug substance impurities are routinely monitored using HPLC. Because HPLC retention times can vary, uncertainty can arise as to whether a p eak at a new retention time is a new impurity. When impurity standards are not available some method is needed to characterize the impuritie s on-line. This work sought to assess the ability of LC/MS/MS to gener ate characteristic impurity 'fingerprints', comprised of a precursor i on mass plus at least three product ion masses. MS/MS fingerprints of a drug substance, DuP 941, and three of its impurities were first gene rated using available standards. Experiments varying collision cell pa rameters showed that collision energy must be specified in order to re producibly generate characteristic MS/MS fingerprints. MS/MS fingerpri nts were also generated on-line for seven impurities in the earliest s afety lot of DuP 941. Several subsequent lots of DuP 941 were examined to see how well their impurity fingerprints matched those from the ea rlier lot. Fingerprint reproducibility was very good for all impuritie s examined, even down to 0.01 UV area percent for some impurities. MS/ MS fingerprinting was able to distinguish two impurities from one anot her which were known to be positional isomers. It also permitted assig nment of tentative structures to the drug impurities. (C) 1998 Elsevie r Science B.V.