title: High-performance liquid chromatographic-electrochemical assay for the quantitation of BMS-181885 in monkey plasma.
abstract: A high-performance liquid chromatographic-electrochemical assay was developed and validated for the quantitation of BMS-181885 (I), an anti-migraine agent, in monkey plasma. The assay involved a solid-phase extraction of I and BMY-46317 (internal standard; I.S.) on a 1-ml cyano cartridge using the automatic solid-phase extraction cartridge (ASPEC) system. Immediately following the conditioning of the cyano column (3 ml of methanol and 2 ml of 1% glacial acetic acid), plasma (0.25 ml) was loaded on to the column. The column was then washed with a 3 ml of 0.1 M ammonium acetate buffer (pH 6). The final elution of the analytes was performed using 2 ml of methanol. The eluate was then evaporated to dryness (gentle stream of nitrogen at 40 degrees C) and the residue was dissolved in the mobile phase and injected on to a YMC basic column (15 cm x 4.6 mm; 5 microm particle size) at a flow-rate of 1 ml/min. A mixture of 0.1 M ammonium acetate at pH 6-acetonitrile-methanol (70:20:10, v/v) was used as the mobile phase. Standard curves, with a lower limit of quantitation of 2 ng/ml of I were linear (r2> or =0.998; range: 2-50 ng/ml). Based on the analysis of the quality control (QC) samples, the assay was both accurate and precise. The stability of I was established following freeze-thaw cycles and storage at or below -20 degrees C. The extraction recovery of I from monkey plasma was about 82%. The validated assay method was applied to determine the pharmacokinetics of I in monkeys following a single 1 mg/kg intravenous dose.
authors.affiliation: Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Srinivas
authors.forename: V R
authors.initials: VR
authors.lastname: Shah
authors.forename: A
authors.initials: A
authors.lastname: Schuster
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.forename: D W
authors.initials: DW
authors.lastname: Whigan
authors.forename: W C
authors.initials: WC
authors.lastname: Shyu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D004563:Electrochemistry / Q000379:methods; D000882:Haplorhini; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D016014:Linear Models; D008881:Migraine Disorders / Q000188:drug therapy; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017366:Serotonin Receptor Agonists / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: C111853:BMS 181885; D007211:Indoles; D010879:Piperazines; D017366:Serotonin Receptor Agonists