Sensitive capillary gas chromatographic-mass spectrometric-selected-ion monitoring method for the determination of diclofenac concentrations in human plasma.
We have modified and validated a capillary GC-MS method reported by Kadowaki et al. [J. Chromatogr., 308 (1984) 329] for the determination of diclofenac in human plasma by using heptane rather than benzene as an extraction agent. In addition, acetone was added to the samples as a deproteination agent which increased the recovery of diclofenac. These revised processes allowed clean extraction and near-quantitative recovery of analyte (> 95%). Separation was achieved on an HP-1 column with helium as carrier gas. The parent ion peaks of diclofenac (m/z 277) and the internal standard, 4'-methoxydiclofenac (m/z 307), were monitored by a mass-selective detector using the selected-ion monitoring mode. The linear range for the routine assay was from 5 to 2000 ng/ml. The detection and lower quantifiable limits were 0.2 and 1 ng/ml, respectively, with no interference from plasma. The within-day and between-day coefficients of variation for high and medium concentrations were less than 5% and were less than 13% for low concentrations (10 ng/ml). This GC-MS assay method has been used for pharmacokinetic and drug interaction studies in humans.
Borenstein
M R
MR
Drug Research Unit, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.
Xue
Y
Y
Cooper
S
S
Tzeng
T B
TB
D000096:Acetone; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood*; D002138:Calibration; D004008:Diclofenac / Q000097:blood*; D016903:Drug Monitoring; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006536:Heptanes; D006801:Humans; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006536:Heptanes; D000096:Acetone; D004008:Diclofenac