Subnanogram-concentration measurement of buprenorphine in human plasma by electron-capture capillary gas chromatography: application to pharmacokinetics of sublingual buprenorphine.
We describe a sensitive and specific method for the measurement of buprenorphine in human plasma. The method involves a structural analog as an internal calibrator, careful control of pH during sample extraction to maximize drug recovery, and back-extraction into acid followed by reextraction to eliminate endogenous interferences. After evaporation, sample residues are derivatized with heptafluorobutyric anhydride and analyzed by separation on a fused-silica polymethylsiloxane capillary column and electron-capture detection. Calibration curves were linear in the ranges 0.1-2.0 micrograms/L and 2.0-20 micrograms/L, with within-run CVs of 9.7% at 0.1 microgram/L to 5.0% at 20 micrograms/L, and total CVs of 15.9% at 0.1 microgram/L to 6.5% at 10 micrograms/L. The limit of quantification was 0.1 microgram/L. The method was utilized in studies to determine the absolute bioavailability of sublingual doses of 2 mg of buprenorphine in 1 mL of 300 mL/L ethanol and the bioequivalence of sublingual 8-mg tablet and 300 mL/L ethanol solution formulations.
Everhart
E T
ET
Department of Psychiatry, University of California, San Francisco 94143, USA.
Cheung
P
P
Shwonek
P
P
Zabel
K
K
Tisdale
E C
EC
Jacob
P
P
Mendelson
J
J
Jones
R T
RT
D000286:Administration, Sublingual; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001682:Biological Availability; D002047:Buprenorphine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002849:Chromatography, Gas; D004355:Drug Stability; D006801:Humans; D007275:Injections, Intravenous; D012680:Sensitivity and Specificity
D000701:Analgesics, Opioid; D002047:Buprenorphine