Simultaneous determination of paracetamol and dextropropoxyphene in human plasma by liquid chromatography/tandem mass spectrometry: application to clinical bioequivalence studies

Abstract

A liquid chromatography/mass spectrometry method for simultaneous determination of paracetamol and dextropropoxyphene in human plasma is described. Paracetamol and dextropropoxyphene, together with their internal standards (tolbutamide and pyrroliphene), were extracted from 0.5 mL of plasma using solid-phase extraction. The chromatography was performed using a Thermo Hypersil APS-2 Amino column (250 mm x 4.6 mm, 5 microm) with a mobile phase consisting of acetonitrile and 0.4% glacial acetic acid in water (20:80). The total run time was 6 min for each sample. The triple-quadrupole mass spectrometer was operated in both positive (for detection of dextropropoxyphene and its IS pyrroliphene) and negative (for detection of paracetamol and its IS tolbutamide) modes using a polarity-switching technique. Multiple reaction monitoring was used for quantification. The method was linear over the concentration range of 0.1-20 microg/mL for paracetamol and 0.5-80 ng/mL for dextropropoxyphene. The intra- and inter-day precision were less than 10%, and the accuracy ranged from 92.2-110.9%. The lower limits of quantification were 0.1 microg/mL for paracetamol and 0.5 ng/mL for dextropropoxyphene. The present method provides a robust, fast and sensitive analytical tool for both paracetamol and dextropropoxyphene, and has been successfully applied to a clinical bioequivalence study in 14 subjects.

Quantification of acetaminophen and two of its metabolites in human plasma by ultra-high performance liquid chromatography–low and high resolution tandem mass spectrometry

“…Crossreactivity that is difficult to predict is also known to potentially affect immunoassays results [13]. For these reasons, in addition to the multi-components quantification capabilities and sensitivity issues, LC-MS/MS methods have been introduced recently for the measurement of APAP in human plasma [14][15][16][17][18][19][20]. As expected, overall better sensitivities than traditional LC-UV platforms [21][22][23] were obtained.…”

Extraction en phase solide de 22 médicaments d'intérêt en toxicologie médico-légale

“…De nombreux protocoles sont publiés pour chacune de ces cartouches, ils ont servi de base à nos travaux [7][8][9][10][11][12][13][14][15][16].…”

“…Pour chaque paramètre, des séries de trois essais ont été exécutées. Tous les tests ont été réali-sés sur des mélanges contenant 6 à 8 molécules choisies de manière à obtenir un tracé chromatographique (figure 1) sans phénomène de co-élution [13,14,16]. Ainsi il a été avéré l'absence d'interférence d'un résultat sur l'autre pour les calculs de rendements d'extraction.…”

Quantification of acetaminophen (paracetamol) in human plasma and urine by stable isotope-dilution GC–MS and GC–MS/MS as pentafluorobenzyl ether derivative

“…In recent years, several LC-MS and LC-MS/MS methods have been reported for the analysis of acetaminophen and its major urinary metabolites, either alone or in combination with other drugs in biological samples (e.g., Refs. [5][6][7][8][9][10][11][12][13]). In contrast, GC-MS methods for acetaminophen are rare.…”