DETERMINATION OF RO-19-6327 (LAZABEMIDE) IN HUMAN PLASMA AND URINE BYGAS-CHROMATOGRAPHY NEGATIVE CHEMICAL-IONIZATION MASS-SPECTROMETRY

A sensitive and specific analytical method was developed for determina tion of Ro 19-6327 (Lazabemide) in human plasma and urine samples to p rovide pharmacokinetic data from clinical trials. The new method emplo ys a simple liquid-liquid extraction to isolate the drug from biologic al samples. The extract is reacted to form the trifluoroacetyl derivat ive of Ro 19-6327 and then analyzed by gas chromatography-negative che mical ionization mass spectrometry (GC-NCIMS). The lower limit of quan titation of the assay is 0.05 ng/ml for plasma and 5.0 ng/ml for urine , based on I-mi aliquots. No interferences from anticoagulants, collec tion devices, or endogenous constituents of plasma and urine were obse rved. Recovery (64.3%), inter-assay precision (<8% R.S.D.), and accura cy (>85%) of the method were considered acceptable. The assay proved r eliable enough to be automated for unattended sample analysis of appro ximately 50 samples daily. In an additional series of tests, Ro 19-632 7 was shown to be stable under conditions that might be encountered du ring the analysis of samples from clinical trials.