title: Simultaneous quantitation of azole antifungals, antibiotics, imatinib, and raltegravir in human plasma by two-dimensional high-performance liquid chromatography-tandem mass spectrometry.
abstract: High-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a standard analytical technique for therapeutic drug monitoring (TDM). A rapid LC-MS/MS method was developed for simultaneous quantitation of 3 antifungals and one active metabolite (posaconazole, voriconazole, itraconazole, and hydroxy-itraconazole), 5 antibiotics (daptomycin, ciprofloxacin, oxacillin, levofloxacin, and rifampicin), an antineoplastic agent (imatinib), and an antiretroviral (raltegravir) in human plasma. Protein precipitation of 10 μL of plasma with acetonitrile was used as a single-extraction procedure. After 2-dimensional LC, all drugs were quantified by electrospray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection in the positive mode. The method was validated per FDA recommendations including the study of extraction recovery (from 79.3% to 105.9%) and matrix effect via ion suppression/enhancement phenomenon. This method is precise (intra- and inter-assay coefficients of variation of 1.95-12.77%, 2.56-8.16% and 2.12-11.38% for low, medium and high levels of internal quality controls respectively) and accurate (intra- and inter-assay biases of 0.19-12.67%, 0.04 to -12.17% and 0.22-12.98% respectively). This method is an efficient tool for routine TDM and optimization of laboratory resource utilization.
authors: CHU, Hôpital A. Michallon, Laboratoire de pharmacologie-toxicologie, BP217, Grenoble F-38043, France. JFJourdil@chu-grenoble.fr
authors: Jean-François
authors: JF
authors: Jourdil
authors: Julia
authors: J
authors: Tonini
authors: Françoise
authors: F
authors: Stanke-Labesque
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood*; D000935:Antifungal Agents / Q000097:blood*; D000970:Antineoplastic Agents / Q000097:blood; D001393:Azoles / Q000097:blood*; D001549:Benzamides / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D000068877:Imatinib Mesylate; D016018:Least-Squares Analysis; D057230:Limit of Detection; D010879:Piperazines / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D011760:Pyrrolidinones / Q000097:blood*; D000068898:Raltegravir Potassium; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001393:Azoles; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D000068877:Imatinib Mesylate