Simple and sensitive liquid chromatography–tandem mass spectrometry methods for quantification of tadalafil in rat plasma: application to pharmacokinetic study in rats

다국어 초록 (Multilingual Abstract)

A simple and sensitive liquid chromatography–tandem mass spectrometry method was developed andvalidated in rat plasma for quantification of tadalafil, anovel therapeutic agent for erectile dysfunction. Tadalafiland acebutolol (internal standard) were extracted byliquid–liquid extraction with tert-butyl methyl ether. Thechromatographic separation was performed on a reversephase C18 column with a mobile phase consisting of 0.1 %formic acid and acetonitrile (45:55, v/v) at a flow rate of0.3 mL/min. The protonated analyte was quantitated bymultiple reaction monitoring with a Waters QuattromicroTM API mass spectrometer. The calibration curve waslinear over a concentration range of 2–2000 ng/mL, and thelower limit of quantification was 2 ng/mL with a precision(CV %) of 10.9 %. Acceptable intra-day and inter-dayprecision and accuracy were obtained at 3 concentrationlevels (3, 200, and 1500 ng/mL). Tadalafil was found to bestable in a battery of studies, including bench top, freeze–thaw, and autosampler conditions. The validated methodwas successfully used to determine tadalafil concentrationin rat plasma samples after oral administration at a dose of1 mg/kg.

참고문헌 (Reference)

1 Bischoff, E., "Vardenafil preclinical trial data: potency, pharmacodynamics, pharmacokinetics, and adverse events" 16 (16): 34-37, 2004

2 Unceta, N., "Validation of an LC-ESI-MS/MS method for the quantitation of phosphodiesterase-5 inhibitors and their main metabolites in rat serum and brain tissue samples" 70 : 529-533, 2012

3 Ali, I., "Validated method for tadalafil analysis in pharmaceutical preparations by capillary electrophoresis" 60 : 187-191, 2004

4 Shakya, A. K., "Validated liquid chromatographic-ultraviolet method for the quantitation of tadalafil in human plasma using liquid–liquid extraction" 852 : 403-408, 2007

5 Martin-Morales, A., "Therapeutic effectiveness and patient satisfaction after 6 months of treatment with tadalafil, sildenafil, and vardenafil: results from the erectile dysfunction observational study (EDOS)" 51 : 541-550, 2007

6 Forgue, S. T., "Tadalafil pharmacokinetics in healthy subjects" 61 : 280-288, 2006

7 Hasegawa, K., "Simultaneous analysis of sildenafil, vardenafil, tadalafil, and their desalkyl metabolites in human whole blood and urine by isotope dilution LC-MS-MS" 30 : 25-32, 2012

8 Ramakrishna, N. V., "Quantitation of tadalafil in human plasma by liquid chromatography-tandem mass spectrometry with electrospray ionization. Journal of Chromatography. B" 809 : 243-249, 2004

9 Seftel, A. D., "Phosphodiesterase type 5 inhibitor differentiation based on selectivity, pharmacokinetic, and efficacy profiles" 27 : 14-19, 2004

10 Wrishko, R. E., "Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects" 48 : 610-618, 2008

11 Spence, R., "No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers" 98 : 4962-4974, 2009

12 Man, C. N., "Identification of sildenafil, tadalafil and vardenafil by gas chromatography-mass spectrometry on short capillary column" 1216 : 8426-8430, 2009

13 Lue, T. F, "Erectile dysfunction" 342 : 1802-1813, 2000

14 Cleves, A. E., "Effects of inductive bias on computational evaluations of ligand-based modeling and on drug discovery" 22 : 147-159, 2008

15 Lee, J. H., "Effects of experimental hyperlipidaemia on the pharmacokinetics of docetaxel in rats" 41 : 797-804, 2011

16 Garraffo, R., "Effect of tipranavir/ritonavir combination on the pharmacokinetics of tadalafil in healthy volunteers" 51 : 1071-1078, 2011

17 Ring, B. J., "Effect of tadalafil on cytochrome P450 3A4-mediated clearance : studies in vitro and in vivo" 77 : 63-75, 2005

18 Nikolaou, P., "Development and validation of a GC/MS method for the determination of tadalafil in whole blood" 56 : 577-581, 2011

19 Cheng, C. L., "Determination of tadalafil in small volumes of plasma by high-performance liquid chromatography with UV detection" 822 : 278-284, 2005

20 Rust, K. Y., "Detection and Validated quantification of the phosphodiesterase type 5 inhibitors sildenafil, vardenafil, tadalafil, and 2 of their metabolites in human blood plasma by LC–MS/ MS-application to forensic and therapeutic drug monitoring cases" 34 : 729-735, 2012

21 Thompson, W. J., "Cyclic nucleotide phosphodiesterases: pharmacology, biochemistry and function" 51 : 13-33, 1991

22 Murad, F, "Cyclic GMP : synthesis, metabolism, and function. Introduction and some historical comments" 26 : 1-5, 1994