کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10553622 | 967878 | 2009 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Rapid resolution liquid chromatography-mass spectrometry determination of SAR97276 in monkey matrices. Pharmacokinetics in rhesus monkey infected by Plasmodium cynomolgi
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Since several years, we developed a new class of antimalarial drugs targeting the phospholipid metabolism of the Plasmodium falciparum malaria parasite. The bis-thiazolium compound, SAR97276, is the lead compound and is now in clinical development. In this paper, we applied the fast rapid resolution liquid chromatography-mass spectrometry technique to the analysis of SAR97276 in monkey matrices. The sample pre-treatment procedure involved an acidic precipitation of proteins followed by solid-phase extraction. The monocationic compound, T2, was used as internal standard. A good separation was achieved on a Zorbax eclipse XDB C8 column (1.8 μm, 50 mm Ã 4.6 mm) with a mobile phase consisting of acetonitrile-trimethylamine-formate buffer (pH 3) gradient elution. The total run time was 8 min. Inter-assay precisions were <10% in plasma, and â¤12% in blood. Accuracies were 96.6-98.1% (plasma) and 94.5-103% (blood). Mean extraction efficiencies were >85% in plasma, and >75% in blood. The lower limits of quantitation were 3.3 μg/l in plasma and 3.3 μg/kg in blood. No matrix effect was observed. This newly developed method is sensitive, selective, reproducible, and stability indicating. It was used to analyse samples taken during a pharmacokinetic/pharmacodynamic study carried out in infected Rhesus monkey by Plasmodium cynomolgi as part of the ongoing development of SAR97276.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 49, Issue 5, 12 July 2009, Pages 1266-1271
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 49, Issue 5, 12 July 2009, Pages 1266-1271
نویسندگان
D. Margout, N. Bontemps, C.H.M. Kocken, H.J. Vial, F.M.M. Bressolle,