title: Simultaneous quantitative analysis of the antimalarials pyrimethamine and sulfamethoxypyrazine in plasma samples using liquid chromatography/tandem mass spectrometry.
abstract: The work presented here deals with the development of a quantitative tool for the simultaneous determination of sulfamethoxypyrazine (sulfalene)/pyrimethamine in plasma. The chromatography used only takes 12.5 min, allowing a fast sample turnover time. Relative standard deviation of retention times was never above 3.48% (n = 66). Adequate sample clean-up was achieved by a simple and relatively fast liquid/liquid extraction. In this way, ionisation suppression effects, typical for more simple sample clean-up procedures, could be avoided resulting in absolute plasma effects of maximum -17.1% for sulfalene, -16.1 for the internal standard (IS), and 12% for pyrimethamine. For both pyrimethamine and sulfalene, quadratic calibration curves from 0.00101 to 0.807 microg/mL for pyrimethamine and from 0.271 to 216 microg/mL for sulfalene gave the best fit. Mean coefficients of determination (R2) were 0.9951 (n = 6, CV% 0.39) for pyrimethamine and 0.9942 (n = 6, CV% 0.13) for sulfalene. Precision was below 9.35% for pyrimethamine and 13.9% for sulfalene. Inaccuracy remained below 15% at all cases. The optimised method was used for a time-course study of the sulfalene/pyrimethamine combination concentration in plasma of patients treated with Co-Arinate, a new curative antimalaria-medicine.
authors.affiliation: Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. michael.storme@ugent.be
authors.forename: Michael L
authors.initials: ML
authors.lastname: Storme
authors.forename: F Herwig
authors.initials: FH
authors.lastname: Jansen
authors.forename: Wim
authors.initials: W
authors.lastname: Goeteyn
authors.forename: Jan F
authors.initials: JF
authors.lastname: Van Bocxlaer
mesh_terms: D000962:Antimalarials / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D011739:Pyrimethamine / Q000097:blood*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013415:Sulfalene / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000962:Antimalarials; D013415:Sulfalene; D011739:Pyrimethamine