Determination of Ro 19-6327 (Lazabemide) in human plasma and urine by gas chromatography-negative chemical ionization mass spectrometry.
A sensitive and specific analytical method was developed for determination of Ro 19-6327 (Lazabemide) in human plasma and urine samples to provide pharmacokinetic data from clinical trials. The new method employs a simple liquid-liquid extraction to isolate the drug from biological samples. The extract is reacted to form the trifluoroacetyl derivative of Ro 19-6327 and then analyzed by gas chromatography-negative chemical ionization mass spectrometry (GC-NCIMS). The lower limit of quantitation of the assay is 0.05 ng/ml for plasma and 5.0 ng/ml for urine, based on 1-ml aliquots. No interferences from anticoagulants, collection devices, or endogenous constituents of plasma and urine were observed. Recovery (64.3%), inter-assay precision (< 8% R.S.D.), and accuracy (> 85%) of the method were considered acceptable. The assay proved reliable enough to be automated for unattended sample analysis of approximately 50 samples daily. In an additional series of tests, Ro 19-6327 was shown to be stable under conditions that might be encountered during the analysis of samples from clinical trials.
Davis
P P
PP
Department of Drug Metabolism and Pharmacokinetics, Hoffmann-La Roche, Nutley, NJ 07110, USA.
Crews
T
T
Bradford
J J
JJ
Edom
R W
RW
D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D010848:Picolinic Acids / Q000097:blood* / Q000652:urine*; D011786:Quality Control; D012680:Sensitivity and Specificity
D010848:Picolinic Acids; C059303:lazabemide