Simultaneous determination of didanosine and its amino acid prodrug, valdidanosine by hydrophilic interaction chromatography coupled with electrospray ionization tandem mass spectrometry: application to a pharmacokinetic study in rats.
A rapid, sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with hydrophilic interaction chromatography has been developed and validated for the simultaneous determination of didanosine and valdidanosine (L-valine amino acid ester prodrug of didanosine) in rat plasma. Solid-phase extraction (SPE) column was employed to extract the analytes from rat plasma, with high extraction recovery (>85%) for both didanosine and valdidanosine. The analytes were then separated by hydrophilic interaction chromatography (HILIC column) and detected by a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source. The method was linear over the concentration ranges of 2-20,000 ng/mL for didanosine and 4-300 ng/mL for valdidanosine. The lower limit of quantitation (LLOQ) of didanosine and valdidanosine was 2 and 4 ng/mL, respectively. The intra-day and inter-day relative standard deviation (RSD) were less than 15% and the relative errors (RE) were all within 15%. Finally, the validated UPLC-MS/MS method was successfully applied to the pharmacokinetic study after either didanosine or valdidanosine orally administrated to the Sprague-Dawley rats.
Yan
Zhongtian
Z
Department of Biopharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Sun
Jin
J
Wang
Jinling
J
Xu
Youjun
Y
Chang
Yannan
Y
Meng
Ping
P
Zhu
Meng
M
Fu
Qiang
Q
Sun
Yongbing
Y
He
Zhonggui
Z
D000284:Administration, Oral; D000596:Amino Acids / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D016049:Didanosine / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D019259:Lamivudine / Q000737:chemistry; D008297:Male; D011355:Prodrugs / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
D000596:Amino Acids; D011355:Prodrugs; C549104:valdidanosine; D019259:Lamivudine; D014633:Valine; D016049:Didanosine