An HPLC-MS/MS method for simultaneous determination of decitabine and its valyl prodrug valdecitabine in rat plasma.
A simple and sensitive HPLC-MS/MS method was developed and validated for the simultaneous determination of decitabine and valdecitabine in rat plasma. The analytes were separated on a C(18) column (150mm×4.6mm, 3.5μm) and a triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI) source was applied for detection. A clean solid-phase extraction procedure with cation exchange cartridge was employed to extract the analytes from rat plasma with high recovery of decitabine (>82%). The calibration curves were linear over a concentration range of 10-10,000ng/mL for decitabine and 5-500ng/mL for valdecitabine. The lower limit of quantitation (LLOQ) of decitabine and valdecitabine was 10 and 5ng/mL, respectively. The intra-day and inter-day precisions were less than 15% and the relative error (RE) was all within ±15%. The validated method was successfully applied to a pharmacokinetics study in rats after either decitabine or valdecitabine orally administrated to the Sprague-Dawley rats.
Department of Biopharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Youxi
Y
Zhang
Jin
J
Sun
Yikun
Y
Gao
Ying
Y
Kong
Youjun
Y
Xu
Weiru
W
Jia
Chuanrong
C
Liao
Peng
P
Zhang
He
H
Lian
Xiaopeng
X
Han
Dongpo
D
Li
Yajie
Y
Geng
Zhonggui
Z
He
D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000077209:Decitabine; D016014:Linear Models; D008297:Male; D011355:Prodrugs / Q000032:analysis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014633:Valine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
D011355:Prodrugs; C582287:valdecitabine; D000077209:Decitabine; D014633:Valine; D001374:Azacitidine