High-performance liquid chromatography/tandem mass spectrometry method for the simultaneous determination of cytarabine and its valyl prodrug valcytarabine in rat plasma.
A sensitive, specific and rapid HPLC-MS/MS method has been developed and validated for the simultaneous determination of cytarabine and valcytarabine (valyl prodrug of cytarabine) in rat plasma in the present study. The analytes were separated on a C18 column (50 mm x 2.1 mm, 1.7 microm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was applied for detection. Cation exchange solid-phase extraction cartridge was employed to extract the analytes from rat plasma, with high recovery of cytarabine (>85%). The method was linear over the concentration ranges of 10-20,000 ng/mL for cytarabine and 25-1000 ng/mL for valcytarabine. The lower limit of quantitation (LLOQ) of cytarabine and valcytarabine was 10 and 25 ng/mL, respectively. The intra-day and inter-day relative standard deviation (RSD) were less than 15% and the relative error (RE) were all within 15%. Finally, the method was successfully applied to support the prodrug pharmacokinetic study after valcytarabine and cytarabine were orally administrated to the Sprague-Dawley rat, respectively.
Sun
Yongbing
Y
Department of Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Sun
Jin
J
Wen
Bing
B
Shi
Shiliang
S
Xu
Youjun
Y
Chen
Ying
Y
Wang
Yongjun
Y
Pan
Changqi
C
Zhang
Chunyu
C
Zhang
Tianhong
T
He
Zhonggui
Z
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry*; D008297:Male; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D011355:Prodrugs; D003561:Cytarabine