Abstract
This study aimed to validate a sensitive and reliable analytical method for the pharmacokinetic study of atomoxetine in human plasma by liquid chromatography-electrospray ionization-tandem mass spectrometry. Metoprolol was used as an internal standard. After liquid-liquid extraction with methyl t-butyl ether, the supernatant was evaporated. The residue was then reconstituted and an aliquot was injected into the high performance liquid chromatographic system. Separation was performed on a Phenomenex Luna C18 column (2.0 mm × 100 mm, 3 μm particles) with a mobile phase of 10 mM ammonium formate buffer: methanol = 10: 90 (v/v). Tandem mass spectrometry was performed in the electrospray ionization positive ion mode using the multiple reaction monitoring mode for quantification. The mass transition pairs of m/z 256 → 44 for atomoxetine and m/z 268 → 116 for the internal standard were used. The flow rate of the mobile phase was 0.25 mL/min and the retention times of atomoxetine and the internal standard were found to be 1.0 and 0.9 min, respectively. The calibration curve for atomoxetine was linear in the concentration range of 1-750 ng/mL (r 2 = 0.9992) with a lower limit of quantification of 1 ng/mL. The mean accuracy for atomoxetine was 93-102%. The coefficients of variation (precision) in the intra- and inter-day validation for atomoxetine were 4.0-6.8 and 1.1-9.6%, respectively. The pharmacokinetic parameters of atomoxetine were evaluated after administration of a 40-mg single oral dose to twelve healthy male volunteers. The mean AUC0-24 h, C max, T max and T 1/2 for atomoxetine were 1.9 ± 0.8 μg h/mL, 0.34 ± 0.11 μg/mL, 1.0 ± 0.5 h and 3.9 ± 1.3 h, respectively.
Original language | English |
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Pages (from-to) | 986-991 |
Number of pages | 6 |
Journal | Journal of Analytical Chemistry |
Volume | 68 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2013 |
Keywords
- atomoxetine
- human plasma
- LC-ESI-MS/MS
- pharmacokinetics