title: Development and Validation of a Sensitive LC-MS-MS Method for the Determination of Adefovir in Human Serum and Urine: Application to a Clinical Pharmacokinetic Study.
abstract: A rapid and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of adefovir (PMEA,9-(2-phosphonylmethoxyethyl) adenine) concentration in human serum and urine. The analysis was performed on a negative ionization electrospray mass spectrometer via multiple reaction monitoring. The monitored transitions were set at m/z 272.0 → 134.0 and m/z 276.0 → 149.8 for PMEA and internal standard, respectively. After protein precipitation, samples were separated by high-performance liquid chromatography on a reversed-phase Dikma Diamonsil C18 (250 × 4.6 mm; 5 µm) column with a mobile phase of 0.1 mM ammonium formate buffer-methanol. The calibration curves were linear over the serum concentration range 0.5-1,000 ng/mL and urine concentration range 2.0-1,000 ng/mL. The intra- and interday precision values of PMEA in both serum and urine were lower than 18.16% for low quality control and 13.70% for medium and high quality control. The accuracy, recovery, matrix factor and stability were also within the acceptable limits. The developed method was successfully applied to the pharmacokinetic study of following oral administration of single dose of pradefovir mesylate (10, 30, 60, 90 and 120 mg) and adefovir dipivoxil (10 mg) to healthy Chinese volunteers.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, Zhongda Hospital of Southeast University, No. 87 Ding Jia Qiao, Nanjing 210009, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Department of Clinical Pharmacy, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Xiao
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, China yjcpu@yahoo.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D063065:Organophosphonates / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D015203:Reproducibility of Results; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; C053001:adefovir; D000225:Adenine