title: Development and application of a simple LC-MS method for the determination of plasma rilpivirine (TMC-278) concentrations.
abstract: Rilpivirine (TMC-278) is a second-generation non-nucleoside reverse transcriptase inhibitor that is high potent against both wild-type and drug-resistant HIV-1 strains. Therefore, rilpivirine is expected to treat therapy-experienced patients who failed to use current drugs due to the emergence of drug-resistant HIV mutants. The quantification of rilpivirine in human plasma is important to support clinical studies and determine pharmacokinetic parameters of rilpivirine in HIV-1 infected patients. Consequently, simple and easy system to determine plasma rilpivirine concentrations has been required. In this study, we developed a conventional LC-MS method to quantify plasma rilpivirine. Subsequently the method was validated by estimating the precision and accuracy for inter- and intraday analysis in the concentration range of 18-715 ng/ml. The calibration curve was linear in this range. Average accuracy ranged from 100.0 to 100.6%. Relative standard deviations of both inter- and intraday assays were less than 3.3%. Recovery of rilpivirine was more than 82.0%. These results demonstrate that our LC-MS method provides a conventional, accurate and precise way to determine rilpivirine in human plasma. This method can be used in routine clinical application for HIV-1 infected patients, and permits management of drug interactions and toxicity for rilpivirine.
authors.affiliation: Department of Pharmacy, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shibata
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Munehiro
authors.initials: M
authors.lastname: Yoshino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuwahara
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Nomura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yokomaku
authors.forename: Wataru
authors.initials: W
authors.lastname: Sugiura
mesh_terms: D019380:Anti-HIV Agents / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009570:Nitriles / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000097:blood*; D000068696:Rilpivirine
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D000068696:Rilpivirine