DETERMINATION OF AN ACETYLCHOLINESTERASE INHIBITOR, MDL-73745, IN DOGPLASMA AND URINE BY COMBINED GAS-CHROMATOGRAPHY NEGATIVE-ION CHEMICAL-IONIZATION MASS-SPECTROMETRY

A highly sensitive and specific assay has been developed for the deter mination of MDL 73745 2,2-trifluoro-1-(3-trimethylsilyl-phenyl)ethanon e] (I) and the internal standard (MDL 74398) at the nanomolar level in dog plasma and urine by gas chromatography/mass spectrometry. After a single-step extraction process, an aliquot was directly injected onto the gas chromatograph column. The mass spectrometer was run in the ne gative ion chemical ionization mode with ammonia as reagent gas, and w as set to monitor the abundant M-. ion at m/z 246 of both compounds. T he method yielded a linear response over the concentration range 0.1-1 0 pmol 100 mul-1 plasma or urine. Within-day reproducibility at a conc entration of 0.25, 1 and 5 pmol 100 mul-1 plasma was 8.6%, 1.0% and 1. 0%, respectively. The method was applied to the determination of I in plasma and urine after administration of 1 mg kg-1 i.v. and 10 mg kg-1 p.o. to dogs.