Quantitative determination of nefopam in human plasma, saliva and cerebrospinal fluid by gas-liquid chromatography using a nitrogen-selective detector.
A sensitive and selective gas-liquid chromatographic method for the determination of nefopam in human plasma, saliva and cerebrospinal fluid has been developed. The method includes the selective extraction of nefopam and the internal standard, orphenadrine, from biological fluids by a double extraction procedure. The extracted nefopam and internal standard are analyzed by a gas chromatograph equipped with a 3% OV-17 glass column and a nitrogen-phosphorus flame ionization detector (NPFID) operated in the nitrogen mode. The detector provides the needed high sensitivity and also selectivity due to the inherent characteristics of NPFID to discriminate against non-nitrogen containing materials. Five nanograms nefopam per ml plasma or saliva are routinely quantitated with a 1-ml sample or as little as 2 ng per ml cerebrospinal fluid with a 3-ml sample. The intra-day reproducibilities, expressed as the relative standard deviation, are 5, 2 and 3% at 10, 35 and 75 ng/ml plasma levels, respectively. The accuracies expressed by relative error at these levels are 12, -4 and -2%, respectively. The inter-day reproducibility is demonstrated by the small relative standard, deviation, 2%, of the slopes from ten plasma standard curves run on ten different days. In various clinical studies in humans the method has been successfully applied to the study of single-dose pharmacokinetics of nefopam and the monitoring of nefopam concentrations in saliva and cerebrospinal fluids.
D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007273:Injections, Intramuscular; D009340:Nefopam / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid; D010079:Oxazocines / Q000097:blood*; D012463:Saliva / Q000032:analysis*; D013997:Time Factors
D010079:Oxazocines; D009340:Nefopam