Development of a rapid and sensitive UPLC-MS/MS assay for the determination of TM-2 in beagle dog plasma and its application to a pharmacokinetic study.
A simple and sensitive method based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of TM-2, which was a novel semi-synthetic taxane derivative in beagle dog plasma. Cabazitaxel was chosen as internal standard. Following extraction by methyl tert-butyl ether, the chromatographic separation was achieved on a Thermo Syncronis C18 column (50 × 2.1 mm, 1.7 µm) by gradient elution within a runtime of 3.5 min. The mobile phase consisted of (A) acetonitrile and (B) 2 mmol/L ammonium acetate in water. The detection was accomplished using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 812.39 → 551.35 for TM-2 and 836.36 → 555.26 for IS, respectively. The method was linear for TM-2 (r = 0.9924) ranging from 2.5 to 1000 ng/mL. The intra-day and inter-day precisions (relative standard deviation) were within 8.0 and 17.6%, respectively, and the accuracy (relative error) was less than 2.3%. The extraction recovery ranged from 83.1 to 97.1%. The reliable method was successfully applied to a pharmacokinetic study of TM-2 in beagle dogs after intravenous drip with different doses of 0.6, 1.2, and 2.4 mg/kg, respectively.
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, People's Republic of China.
Hongli
H
Lin
Yunli
Y
Zhao
Lei
L
Men
Mingjing
M
Yang
Hui
H
Liu
Yanjie
Y
Shao
Pei
P
Wang
Xing
X
Tang
Zhiguo
Z
Yu
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D043823:Taxoids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*
C000593048:13-(N-tert-butoxycarbonyl-3-isobutylisoserinoyl-4,10-diacetoxy-2-benzoyloxy-5-20-epoxy-1,13-dihydroxy-9-oxo-19-norcyclopropa(g)tax-11-ene; D043823:Taxoids
TM-2; UPLC-MS/MS; beagle dog plasma; pharmacokinetics; taxane