Stable isotope dilution negative ion chemical ionization gas chromatography-mass spectrometry for the quantitative analysis of paroxetine in human plasma.
A sensitive and specific method for the quantitative determination of paroxetine in human plasma is presented. After solvent extraction from plasma with hexane/ethyl acetate (1 : 1) at alkaline pH and derivatization to the pentafluorobenzyl carbamate derivative, paroxetine was measured by gas chromatography-negative ion chemical ionization mass spectrometry. The carboxylate anion at m/z 372 was obtained at high relative abundance. [2H6]-labeled paroxetine was used as an internal standard and its rapid and facile preparation from the unlabeled compound is described. Calibration graphs were linear within a range of 0.094-12.000 ng x ml(-1) using 1 ml of plasma and 0.469-60 ng x ml(-1) using 200 microl of plasma. Intra-day precision was 1.47% (0.375 ng x ml(-1)), 3.16% (3 ng x ml(-1)) and 1.37% (9 ng x ml(-1)) for the low-level method, and 3.37% (1.875 ng x ml(-1)), 2.72% (15 ng x ml(-1)) and 2.22% (45 ng x ml(-1)) for the high-level method. Inter-day precision was 1.65% (0.375 ng x ml(-1)), 2.13% (3 ng x ml(-1)) and 1.66% (9 ng x ml(-1)) for the low-level method, and 1.10% (1.875 ng x ml(-1)), 1.56% (15 ng x ml(-1)) and 1.90% (45 ng x ml(-1)) for the high-level method. At the limit of quantification (0.094 ng x ml(-1)), intra-day precision was 4.30% (low-level method) and 2.56% (high-level method), and inter-day precision was 3.23% (low-level method) and 3.00% (high-level method). The method is rugged, rapid and robust and has been applied to the batch analysis of paroxetine during pharmacokinetic profiling of the drug.
Leis
H J
HJ
University Children's Hospital, Division of Analytical Biochemistry and Mass Spectrometry, Auenbruggerplatz 30, A-8036 Graz, Austria. hans.leis@kfunigraz.ac.at
Windischhofer
W
W
Raspotnig
G
G
Fauler
G
G
D002138:Calibration; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D017374:Paroxetine / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012997:Solvents
D012997:Solvents; D017374:Paroxetine; D003903:Deuterium