Hydrophilic interaction liquid chromatography-tandem mass spectrometry for the determination of adefovir in human plasma and its application to a pharmacokinetic study.
A selective, rapid and sensitive hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method was developed for the first time to determine adefovir in human plasma and applied to a pharmacokinetic study. Plasma samples were prepared by protein precipitation with methanol followed by a further cleaning using dichloromethane. The chromatographic separation was carried out on an ACQUITY UPLC BEH HILIC column with the mobile phase of methanol-water-formic acid (85:15:0.2, v/v/v). The detection was performed on a triple-quadrupole tandem mass spectrometer with multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The method was rapid with a run time of 3 min per sample. The linear calibration curves were obtained in the concentration range of 1.02-102 ng/mL (r(2)> or =0.99) with the lower limit of quantification (LLOQ) of 1.02 ng/mL. The intra- and inter-day precision (relative standard deviation, R.S.D.) values were below 12% and the accuracy (relative error, R.E.) was from 0.6% to 3.2% at all quality control (QC) levels. The method was applicable to clinical pharmacokinetic study of adefovir in healthy volunteers after oral administration of adefovir dipivoxil tablet.
Xiong
Zhili
Z
Department of Analytical Chemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
Zhang
Yi
Y
Qin
Feng
F
Qin
Ting
T
Yang
Shuyan
S
Li
Famei
F
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D057230:Limit of Detection; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D053778:Thiazolidines / Q000097:blood / Q000737:chemistry; D013997:Time Factors
D000998:Antiviral Agents; D063065:Organophosphonates; D053778:Thiazolidines; C053001:adefovir; C064893:pidotimod; D000225:Adenine; D011761:Pyrrolidonecarboxylic Acid