title: Determination of SR 49059 in human plasma and urine by LC-APCI/MS/MS.
abstract: SR 49059 ((2S 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3, 4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1 H-indole-2-carbonyl]-pyrrolidine-2-carboxamide) is an orally active non-peptide vasopressin V1a antagonist. A sensitive, selective, and robust LC-MS/MS method was developed to determine the plasma and urine concentrations of SR 49059 in support of clinical studies. Plasma samples were prepared based on a rapid extraction procedure using Chem Elut cartridges. The extracted samples were analyzed on a C18 HPLC column interfaced with a Finnigan TSQ 700 mass spectrometer. Positive atmospheric chemical ionization (APCI) was employed as the ionization source. The analyte and its internal standard (2H6-SR 49059) were detected by use of multiple reaction monitoring (MRM) mode. The plasma matrix had a calibration range 0.2-20 ng ml-1, with within and between run accuracy and precision both less than 10%. The chromatographic run time was approximately 3 min. Urine samples were prepared based on a simple dilution with water, followed by analysis under the same conditions as plasma. The calibration range for urine matrix was 20-5000 ng ml-1, with within and between run accuracy and precision less than 11%. The method has been successfully applied to the clinical sample analysis. The plasma assay was also evaluated on a Finnigan TSQ 7000 mass spectrometer. The performance based on precision and accuracy was virtually identical to that on the TSQ 700, with the exception of linearity in calibration curve (the TSQ 700 was linear, the TSQ 7000 was quadratic).
authors.affiliation: Sanofi Winthrop Pharmaceutical Research Division, Malvern, PA 19355, USA.
authors.forename: R
authors.initials: R
authors.lastname: Burton
authors.forename: M
authors.initials: M
authors.lastname: Mummert
authors.forename: J
authors.initials: J
authors.lastname: Newton
authors.forename: R
authors.initials: R
authors.lastname: Brouard
authors.forename: D
authors.initials: D
authors.lastname: Wu
mesh_terms: D065092:Antidiuretic Hormone Receptor Antagonists; D001274:Atmospheric Pressure; D002138:Calibration; D002853:Chromatography, Liquid; D003903:Deuterium; D004355:Drug Stability; D006727:Hormone Antagonists / Q000032:analysis* / Q000097:blood / Q000652:urine; D006801:Humans; D007211:Indoles / Q000032:analysis* / Q000097:blood / Q000652:urine; D013058:Mass Spectrometry; D011759:Pyrrolidines / Q000032:analysis* / Q000097:blood / Q000652:urine; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D007211:Indoles; D011759:Pyrrolidines; D003903:Deuterium; C082134:relcovaptan