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Liu M.-S.,Beijing Institute of Pharmacology and Toxicology | Liu M.-S.,Shenyang Pharmaceutical University | Guo J.-F.,Beijing Institute of Pharmacology and Toxicology | Yi H.,Institution of Medicinal Biotechnology | And 3 more authors.

Tenofovir octadecyloxyethyl ester (TOE) is a novel ester prodrug of tenofovir. It is currently developed as a promising antiviral preclinical candidate. A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been developed and validated to quantify TOE in rat plasma. The method involves a simple extraction of TOE and loratadine (internal standard) from rat plasma after protein precipitation. Chromatographic separation was performed on a C18 column by isocratic elution with acetonitrile and 5 mM ammonium acetate containing 0.03% ammonium hydroxide (70:30, v/v), at a flow rate of 0.3 mL min-1. MS detection was performed on an API 3000 triple quadrupole mass spectrometer operating in ESI positive ionization mode. Ions monitored in the multiple selected reaction monitoring mode were m/z 584→270 for TOE and m/z 383→337 for loratadine, respectively. A linear calibration curve was established over the concentration range from 12.5 to 2,500 ng mL-1 (r 2 = 0.9961) with the lower quantitative limit of 12.5 ng mL-1. The inter- and intra-day RSD were all <9.61%, while the accuracy (RE) was within the range from -8.40 to 4.20%. This novel method has been successfully applied to a pharmacokinetic study to obtain the oral concentration-time profile of TOE in rats. © 2011 Springer-Verlag. Source

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