Simultaneous quantitative analysis of the antimalarials pyrimethamine and sulfamethoxypyrazine in plasma samples using liquid chromatography/tandem mass spectrometry

• Published in: Rapid communications in mass spectrometry 2006-01, Vol.20 (19), p.2947-2953
• Main Authors: Storme, Michael L., Jansen, F. Herwig, Goeteyn, Wim, Van Bocxlaer, Jan F.
• Format: Article
• Language: English
• Subjects: Antimalarials - blood; Chromatography, High Pressure Liquid; Pyrimethamine - blood; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization - methods; Sulfalene - blood; Tandem Mass Spectrometry - methods
• ISSN: 0951-4198; 1097-0231
• DOI: 10.1002/rcm.2670

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 µg/mL for pyrimethamine and from 0.271 to 216 µg/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. Copyright © 2006 John Wiley & Sons, Ltd.