Determination of adefovir in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study

Abstract

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated to determine the concentrations of adefovir [9-(2-phosphonylmethoxyethyl)adenine, PMEA] in human plasma. After one-step protein precipitation of plasma samples by methanol, adefovir was analyzed by LC/MS/MS using positive electrospray ionization. Chromatography was performed on a C18 column. The extraction recoveries of adefovir were found to be 85.1-89.3%. Adefovir was stable under routine laboratory conditions. A minimal matrix effect resulting in a slight ionization enhancement of adefovir (<10.9%) was observed, which did not markedly affect the behavior of the calibrations curves and accuracy and precision data. The method had a chromatographic run time of 7.8 min and a linear calibration curve over the concentration range 1.5-90 ng/mL for adefovir. The lower limit of quantification of the method was 1.5 ng/mL. The intra- and inter-day precision was less than 8.4%. These results indicated that this LC/MS/MS method has high selectivity and efficiency, and acceptable accuracy, precision and sensitivity. The validated LC/MS/MS method has been successfully used in a pharmacokinetic study in healthy volunteers treated with oral adefovir dipivoxil at 10 and 20 mg.

HPLC method for determination of in vitro delivery through and into porcine skin of adefovir (PMEA)

“…Several chromatographic methods have been used for the determination of PMEA in biological samples including UV detection [9][10][11], fluorescence detection of derivatized PMEA [12][13][14], radiochromatography [15], and highly sensitive liquid chromatography-tandem mass spectrometry methods [16,17]. None of them, however, focused on the skin as the biological matrix.…”

Simultaneous determination of mifepristone and monodemethyl‐mifepristone in human plasma by liquid chromatography–tandem mass spectrometry method using levonorgestrel as an internal standard: application to a pharmacokinetic study

“…Absolute and relative matrix effect (ME) on the spectral response of IS and analytes was assessed using the procedure described by Matuszewski et al (2003) and Bi et al (2005). Briefly, blank plasma were extracted following SPE procedure and then spiked with the analyte at QC concentrations.…”

Quantitative determination of total methamphetamine and active metabolites in rat tissue by liquid chromatography with tandem mass spectrometric detection

“…Despite this advantage, LLE is not a popular means of biological sample preparation as shown by a search of recent literature. [41][42][43][44] This dissatisfaction with LLE is likely because of the labor-intensive nature of the technique. While there are automated LLE systems commercially available, it is necessary to purchase components from several manufacturers, 45 , 46 and automated control of these components with a single data system is not trivial.…”