TY - JOUR T1 - Development of a fast and simple liquid chromatography-tandem mass spectrometry method for the quantitation of argatroban in patient plasma samples. AU - Rhea,Jeanne M, AU - Snyder,Marion L, AU - Winkler,Anne M, AU - Abou-Diwan,Charbel, AU - Fantz,Corinne R, AU - Ritchie,James C, AU - Szlam,Fania, AU - Tanaka,Kenichi A, AU - Molinaro,Ross J, Y1 - 2012/03/03/ PY - 2011/11/16/received PY - 2012/02/15/revised PY - 2012/02/23/accepted PY - 2012/3/20/entrez PY - 2012/3/20/pubmed PY - 2012/7/27/medline SP - 168 EP - 72 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J Chromatogr B Analyt Technol Biomed Life Sci VL - 893-894 N2 - An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the direct measurement of argatroban in human plasma was developed and compared with the activity-based Hemoclot Thrombin Inhibitors assay. UPLC-MS/MS was performed using diclofenac as an internal standard. In summary, argatroban and diclofenac were extracted from 100 μL of plasma using a methanol precipitation protocol, and chromatographic separation was performed on an ACQUITY TQD mass spectrometer using a UPLC C18 BEH 1.7 μm column with a water and methanol gradient containing 0.1% formic acid. The detection and quantitation were performed using positive ion electrospray ionization and multiple reaction monitoring (MRM) mode. The UPLC-MS/MS method was linear over the concentration range of 0.003-3.0 μg/mL, with a lower limit of quantitation for argatroban of 0.003 μg/mL. The intra- and inter-assay imprecision was less than 12% at the plasma argatroban concentrations tested. Good correlation was demonstrated between the UPLC-MS/MS method and the indirect activity-based assay for determination of argatroban. However, increased plasma fibrinogen levels caused underestimation of argatroban levels using the indirect activity-based assay, whereas the UPLC-MS/MS method was unaffected. UPLC-MS/MS provides a relatively simple, sensitive, and rapid means of argatroban monitoring. It has successfully been applied to assess plasma argatroban concentrations in hospitalized patients and may provide a more accurate determination of argatroban concentrations than an activity-based assay in certain clinical conditions. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/22425273/Development_of_a_fast_and_simple_liquid_chromatography_tandem_mass_spectrometry_method_for_the_quantitation_of_argatroban_in_patient_plasma_samples_ DB - PRIME DP - Unbound Medicine ER -