Development and validation of a highly sensitive LC-ESI-MS/MS method for the determination of Orteronel® (TAK-700) in rat plasma: application to a pharmacokinetic study.
BACKGROUND
A highly sensitive, specific and high-throughput LC-ESI-MS/MS method in the positive mode has been developed and validated for the quantitation of Orteronel® (TAK-700) in rat plasma using YM-55208 as an internal standard.


RESULTS
The assay procedure involves extraction of Orteronel and internal standard from rat plasma with liquid-liquid extraction method. Chromatographic separation was achieved using an isocratic mobile phase at a flow rate of 0.6 ml/min on an Atlantis dC18 column with a total run time of 2.5 min. The MS/MS ion transitions monitored were m/z 308.4→95.0 for Orteronel and m/z 262.3→194.2 for IS. Method validation was performed as per US FDA guidelines. The LLOQ achieved was 0.42 ng/ml and the linearity range extended from 0.42 to 814 ng/ml.


CONCLUSIONS
The results met the acceptance criteria. The validated method was successfully applied to characterize the pharmacokinetic parameters of Orteronel in rat plasma.
Drug Metabolism & Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560 022, India.
Sandip
S
Gurav
Anitha
A
Police
Mohd
M
Zainuddin
Junaid Hassan
JH
Farooqui
Krishna
K
Reddy G
Raghava Reddy
RR
Kethiri
Sriram
S
Rajagopal
Ramesh
R
Mullangi
D000818:Animals; D056148:Chromatography, Reverse-Phase / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D017408:Guidelines as Topic; D006801:Humans; D007093:Imidazoles / Q000097:blood* / Q000493:pharmacokinetics; D057230:Limit of Detection; D016014:Linear Models; D059625:Liquid-Liquid Extraction / Q000379:methods; D008297:Male; D009281:Naphthalenes / Q000097:blood* / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014481:United States; D014486:United States Food and Drug Administration
D007093:Imidazoles; D009281:Naphthalenes; C571806:orteronel