Determination of diclofenac in human plasma by selected ion monitoring.
A simple and rapid gas chromatographic/mass spectrometric method to determine plasma diclofenac was developed, which employs formation of the methyl ester with diazomethane. Methoxydiclofenac was used as the internal standard. Under the conditions used, the previously described partial cyclization of diclofenac to the indolone derivative was avoided. The limit of detection of plasma levels of diclofenac is 2 ng ml-1, which renders the method useful for clinical studies on oral, intravenous and rectal administration of the drug. The analysis is carried out by electron impact gas chromatography/mass spectrometry and can therefore be performed on the more common mass spectrometers. Linearity and reproducibility of the method were demonstrated by the high correlation coefficient of the calibration lines (r greater than 0.999) and from the low variation of their slopes (coefficient of variation 3%) determined on different days, respectively. Pharmacokinetic parameters (area under curve = 1.8 +/- 0.26 microgram h ml-1, tmax = 1.5 +/- 0.5 h, Cmax = 734 +/- 82 ng ml-1 and terminal half-life = 0.88 +/- 0.52 h) determined from the plasma decay of diclofenac in three healthy subjects given a single oral dose of diclofenac were in good agreement with those reported in the literature.
Department of Medical Chemistry and Biochemistry, University of Milan, Italy.
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M
Del Puppo
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Cighetti
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MG
Kienle
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R
Paroni
C
C
Borghi
D001711:Biotransformation; D004008:Diclofenac / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007202:Indicators and Reagents; D012996:Solutions
D007202:Indicators and Reagents; D012996:Solutions; D004008:Diclofenac