Validation and application of a sensitive assay for butorphanol in human plasma by high-performance liquid chromatography with tandem mass spectrometry detection.
A sensitive and convenient high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for the opioid receptor agonist-antagonist butorphanol in human plasma is described. BC-2605, a cyclopropyl analogue of butorphanol, was employed as an internal standard. Butorphanol was recovered from plasma (84.4 +/- 10.9%) by liquid-liquid extraction. The mobile phase flow-rate was 0.3 ml/min and consisted of methanol-water-formic acid (90:10:0.1, v/v/v). The analytical column (4.6 x 100 mm) was packed with Partisil C(8) (5 microm). The standard curve was linear from 13.7 to 1374 pg/ml (r(2)>0.99). The lower limit of quantitation was 13.7 pg/ml. The assay was specific, accurate (% deviation from nominal concentrations were <15%), precise and reproducible (within- and between-day coefficients of variation <7%). Butorphanol in plasma was stable over 3 freeze/thaw cycles and at room temperature for 1 day. The utility of the assay was demonstrated by following butorphanol plasma concentrations in two healthy subjects for 24 h following a 1 mg intranasal dose.
Boulton
David W
DW
Clinical Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA. david.boulton@bms.com
Duncan
Glenn F
GF
Vachharajani
Nimish N
NN
D000328:Adult; D000701:Analgesics, Opioid / Q000097:blood* / Q000493:pharmacokinetics; D002077:Butorphanol / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000701:Analgesics, Opioid; D002077:Butorphanol