title: Development and validation of an RP-HPLC method for the quantitation of Orteronel (TAK-700), a CYP17A1 enzyme inhibitor, in rat plasma and its application to a pharmacokinetic study.
abstract: A novel, simple, specific, sensitive and reproducible high-performance liquid chromatography assay method has been developed and validated for the estimation of Orteronel in rat plasma. The bioanalytical procedure involves extraction of Orteronel and phenacetin (internal standard) from rat plasma with a simple liquid-liquid extraction process. The chromatographic analysis was performed on a Waters Alliance system using a gradient mobile phase conditions at a flow rate of 1 mL/min and a C18 column maintained at ambient room temperature. The eluate was monitored using a photodiode array detector set at 242. Orteronel and internal standard eluted at 4.8 and 6.2 min, respectively and the total run time was 9 min. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 100-3149 ng/mL (r(2) = 0.995). The intra- and inter-day precisions were in the ranges of 0.31-7.87 and 3.97-6.35, respectively, in rat plasma. The validated HPLC method was successfully applied to a pharmacokinetic study of Orteronel in rats.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560 022, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Kumar
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: S
authors.forename: Sandip
authors.initials: S
authors.lastname: Gurav
authors.forename: Mohd
authors.initials: M
authors.lastname: Zainuddin
authors.forename: Purushottam
authors.initials: P
authors.lastname: Dewang
authors.forename: Raghava Reddy
authors.initials: RR
authors.lastname: Kethiri
authors.forename: Sriram
authors.initials: S
authors.lastname: Rajagopal
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mullangi
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase; D004355:Drug Stability; D007093:Imidazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D009281:Naphthalenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors
chemical_list: D007093:Imidazoles; D009281:Naphthalenes; C582555:CYP17A1 protein, rat; D013254:Steroid 17-alpha-Hydroxylase; C571806:orteronel
keywords: HPLC; Orteronel; method validation; pharmacokinetics; rat plasma