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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

New Metabolites of Udenafil Identified through Liquid Chromatography– Quadrupole Time-of-flight Mass Spectrometry

Author(s): Jaesung Pyo*

Volume 17, Issue 8, 2021

Published on: 07 December, 2020

Page: [1000 - 1007] Pages: 8

DOI: 10.2174/1573412917666201208114954

Abstract

Background: Udenafil, a recently discovered drug used for erectile dysfunction treatment, has been widely prescribed and its effect on human systems has been extensively studied. However, there is little research on the human metabolites of udenafil. Three metabolites have been identified in rats.

Objective: Herein, highly sensitive and accurate liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (LC-Q-TOF-MS/MS) was conducted to identify new udenafil metabolites.

Methods: Human liver microsomes were incubated with udenafil for in vitro samples, and rat urine and faeces samples were collected from udenafil-administered rats for in vivo samples. Each sample was deproteinated with acetonitrile and extracted by solid phase extraction. The purified samples were separated and analyzed by LC-Q-TOF-MS, and some metabolite candidates were reanalyzed for further structural analysis using LC-Q-TOF-MS/MS.

Results: Eleven and three metabolites were identified in the in vitro and in vivo samples, respectively, and were found to be hydrolyzed, oxidized, or demethylated forms of udenafil or its metabolites. The error of the metabolic analysis was −8.7 to 7.6 ppm, indicating the high accuracy of the method.

Conclusion: These metabolic results could be useful for further investigation of udenafil and new phosphodiesterase-5 inhibitors.

Keywords: Udenafil, metabolites, LC-Q-TOF-MS/MS, erectile dysfunction, analysis, accuracy, rat urine and faeces, human liver microsome.

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Graphical Abstract
[1]
McVary, K.T.; Carrier, S.; Wessells, H. Subcommittee on Smoking and Erectile Dysfunction Socioeconomic Committee. Sexual Medicine Society of North America. Smoking and erectile dysfunction: evidence based analysis. J. Urol., 2001, 166(5), 1624-1632.
[http://dx.doi.org/10.1016/S0022-5347(05)65641-8] [PMID: 11586190]
[2]
Kubin, M.; Wagner, G.; Fugl-Meyer, A.R. Epidemiology of erectile dysfunction. Int. J. Impot. Res., 2003, 15(1), 63-71.
[http://dx.doi.org/10.1038/sj.ijir.3900949] [PMID: 12605242]
[3]
Rosen, R.; Altwein, J.; Boyle, P.; Kirby, R.S.; Lukacs, B.; Meuleman, E.; O’Leary, M.P.; Puppo, P.; Robertson, C.; Giuliano, F. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur. Urol., 2003, 44(6), 637-649.
[http://dx.doi.org/10.1016/j.eururo.2003.08.015] [PMID: 14644114]
[4]
Billups, K.L. Sexual dysfunction and cardiovascular disease: integrative concepts and strategies. Am. J. Cardiol., 2005, 96(12B), 57M-61M.
[http://dx.doi.org/10.1016/j.amjcard.2005.10.007] [PMID: 16387569]
[5]
Brown, J.S.; Wessells, H.; Chancellor, M.B.; Howards, S.S.; Stamm, W.E.; Stapleton, A.E.; Steers, W.D.; Van Den Eeden, S.K.; McVary, K.T. Urologic complications of diabetes. Diabetes Care, 2005, 28(1), 177-185.
[http://dx.doi.org/10.2337/diacare.28.1.177] [PMID: 15616253]
[6]
McVary, K.T. Erectile dysfunction and lower urinary tract symptoms secondary to BPH. Eur. Urol., 2005, 47(6), 838-845.
[http://dx.doi.org/10.1016/j.eururo.2005.02.001] [PMID: 15925081]
[7]
McVary, K.T. Clinical practice. Erectile dysfunction. N. Engl. J. Med., 2007, 357(24), 2472-2481.
[http://dx.doi.org/10.1056/NEJMcp067261] [PMID: 18077811]
[8]
Kupelian, V.; Shabsigh, R.; Araujo, A.B.; O’Donnell, A.B.; McKinlay, J.B. Erectile dysfunction as a predictor of the metabolic syndrome in aging men: results from the Massachusetts Male Aging Study. J. Urol., 2006, 176(1), 222-226.
[http://dx.doi.org/10.1016/S0022-5347(06)00503-9] [PMID: 16753405]
[9]
Cho, M.C.; Paick, J.S. Udenafil for the treatment of erectile dysfunction. Ther. Clin. Risk Manag., 2014, 10, 341-354.
[PMID: 24868160]
[10]
Rosen, R.C.; Riley, A.; Wagner, G.; Osterloh, I.H.; Kirkpat Rick, J.; Mishra, A. The international index of erectile func tion. Urology, 1997, 49(6), 822-830.
[http://dx.doi.org/10.1016/S0090-4295(97)00238-0] [PMID: 9187685]
[11]
Jr, E.D.M.C.H.N.; Abdo, E.B.; Torres, C.F.L.; Lôbo, J.A.S. Fittipaldi, Prevalence and correlates of erectile dysfunc Tion: results of the Brazilian study of sexual behaviour. Urology, 2001, 58(4), 583-588.
[http://dx.doi.org/10.1016/S0090-4295(01)01274-2] [PMID: 11597544]
[12]
Chung, W.S. Pharmacological management of male sexual Dysfunction. J. Korean Med. Assoc., 2008, 51(8), 770-778.
[http://dx.doi.org/10.5124/jkma.2008.51.8.770]
[13]
Bell, A.S.; Palmer, M.J. Novel phosphodiesterase type 5 modulators: a patent survey (2008 - 2010). Expert Opin. Ther. Pat., 2011, 21(10), 1631-1641.
[http://dx.doi.org/10.1517/13543776.2011.614435] [PMID: 21905762]
[14]
Yuan, J.; Zhang, R.; Yang, Z.; Lee, J.; Liu, Y.; Tian, J.; Qin, X.; Ren, Z.; Ding, H.; Chen, Q.; Mao, C.; Tang, J. Comparative effectiveness and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction: a systematic review and network meta-analysis. Eur. Urol., 2013, 63(5), 902-912.
[http://dx.doi.org/10.1016/j.eururo.2013.01.012] [PMID: 23395275]
[15]
Mehrotra, N.; Gupta, M.; Kovar, A.; Meibohm, B. The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5 inhibitor therapy. Int. J. Impot. Res., 2007, 19(3), 253-264.
[http://dx.doi.org/10.1038/sj.ijir.3901522] [PMID: 16988721]
[16]
Paick, J.S.; Kim, S.W.; Yang, D.Y.; Kim, J.J.; Lee, S.W.; Ahn, T.Y.; Choi, H.K.; Suh, J.K.; Kim, S.C. The efficacy and safety of udenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction. J. Sex. Med., 2008, 5(4), 946-953.
[http://dx.doi.org/10.1111/j.1743-6109.2007.00723.x] [PMID: 18221288]
[17]
Choi, S.J.; Ji, H.Y.; Lee, H.Y.; Kim, D.S.; Kim, W.B.; Lee, H.S. In vitro metabolism of a novel phosphodiesterase-5 inhibitor DA-8159 in rat liver preparations using liquid chromatography/electrospray mass spectrometry. Biomed. Chromatogr., 2002, 16(6), 395-399.
[http://dx.doi.org/10.1002/bmc.173] [PMID: 12228896]

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