A sensitive LC-MS/MS method for quantification of a nucleoside analog in plasma: Application to in vivo rat pharmacokinetic studies

作者：Heudi Olivier^*; Barteau Samuel; Picard Franck; Kretz Olivier

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2009, 877(20-21): 1887-1893.

DOI：10.1016/j.jchromb.2009.05.015

• Nucleoside analogs
• LC-MS/MS
• Polar compounds
• TFA
• Validation and pharmacokinetic

A LC-MS/MS method was developed and validated for determination of nucleoside analog (NA) in rat plasma. The method run time was 6 min and the limit of quantification (LOQ) was estimated at 100 pg/mL The extraction procedure consisted on plasma samples protein precipitation with an acetonitrile solution which contained the stable isotope labeled internal standard (IS). Chromatography was performed on a newly developed C(16) column (150 mm x 4.6 mm, 5 mu m) in order to avoid the use ion pair salts. The samples were eluted at 0.8 mL/min with a gradient of mobile phase made of water and acetonitrile both acidified with 0.5% acetic acid and 0.025% trifluoroacetic acid (TFA). A tandem mass spectrometer was used as a detector for quantitative analysis. Intra-run and inter-run precision and accuracy within +/- 15% were achieved during a 3-run validation for quality control samples at four concentration levels in rat plasma, over a concentration ranging between 0.1 and 1000 ng/mL. The data indicate that our LC-MS/MS assay is an effective method for the pharmacokinetics study of NA in rat plasma.

• 出版日期2009-7-1