title: A rugged and accurate liquid chromatography-tandem mass spectrometry method for quantitative determination of BMS-790052 in plasma.
abstract: To support toxicokinetic assessments, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of BMS-790052 in rat, dog, monkey, rabbit and mouse K(2)EDTA plasma. The drug was isolated from buffered samples using ISOLUTE C8 96-well solid phase extraction (SPE) plates. Chromatographic separation was achieved on a Waters Atlantis dC18 analytical column (2.1 mm × 50 mm, 5 μm) with detection accomplished using an API 4000 tandem mass spectrometer in positive ion electrospray and multiple reaction monitoring (MRM) mode. The standard curves, which ranged from 5.00 to 2000 ng/mL for BMS-790052, were fitted to a 1/x(2) weighted linear regression model. The intra-assay precision (%CV) and inter-assay precision (%CV) were within 8.5%, and the assay accuracy (%Dev) was within ±7.1 for rat, dog, monkey, rabbit and mouse K(2)EDTA plasma. This accurate, precise, and selective SPE/LC-MS/MS method has been successfully applied to analyze several thousands of non-clinical study samples.
authors.affiliation: Bioanalytical Sciences Department, Bristol-Myers Squibb Company, Princeton, NJ 08540, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Jianing
authors.initials: J
authors.lastname: Zeng
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Deng
authors.forename: Yuan-Qin
authors.initials: YQ
authors.lastname: Xia
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ouyang
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jemal
authors.forename: Theodora W
authors.initials: TW
authors.lastname: Salcedo
authors.forename: Mark E
authors.initials: ME
authors.lastname: Arnold
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002219:Carbamates; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D004355:Drug Stability; D015507:Drugs, Investigational; D005260:Female; D000882:Haplorhini; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D051379:Mice; D011759:Pyrrolidines; D011817:Rabbits; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D015507:Drugs, Investigational; D007093:Imidazoles; D011759:Pyrrolidines; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir