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Current Pharmaceutical Analysis

Editor-in-Chief

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

Research Article

Metabolic Study of Benzamidenafil using Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry

Author(s): Jaesung Pyo*

Volume 18, Issue 6, 2022

Published on: 11 March, 2022

Page: [608 - 613] Pages: 6

DOI: 10.2174/1573412918666220202114128

Price: $65

Abstract

Background: Various illegal phosphodiesterase-5 (PDE5) inhibitors have been indiscriminately added to food and dietary supplements since the early 2000s without evaluating their side effects or pharmaceutical effects.

Objective: The metabolic pathway of benzamidenafil was evaluated using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS).

Methods: In vitro metabolic samples were prepared using human liver microsomes, and in vivo metabolic samples were obtained from drug-administered rats. The metabolic samples were extracted to remove biological interferences and injected into the LC-Q-ToF-MS system for analysis. Their mass spectra and chromatograms were compared and interpreted.

Results: A total of nine metabolites were evaluated in the benzamidenafil-treated samples. All error values were within 5 ppm with high accuracy.

Conclusion: These newly identified metabolites of benzamidenafil could be used to construct relevant legal databases and applied to related forensic cases.

Keywords: Benzamidenafil, metabolic profile, LC-Q-TOF-MS, forensic toxicology, forensic chemistry, illegal compounds.

Graphical Abstract

[1]
Patel, D.N.; Li, L.; Kee, C.L.; Ge, X.; Low, M.Y.; Koh, H.L. Screening of synthetic PDE-5 inhibitors and their analogues as adulterants: Analytical techniques and challenges. J. Pharm. Biomed. Anal., 2014, 87, 176-190.
[http://dx.doi.org/10.1016/j.jpba.2013.04.037] [PMID: 23721687]
[2]
Wespes, E.; Amar, E.; Hatzichristou, D.; Montorsi, F.; Pryor, J.; Vardi, Y. European Association of Urology. Guidelines on erectile dysfunction. Eur. Urol., 2002, 41(1), 1-5.
[http://dx.doi.org/10.1016/S0302-2838(01)00008-2] [PMID: 11999460]
[3]
Bakota, E.L.; Kelly, A.T.; Walterscheid, J.P.; Phatak, D.R. A case report of fatal desmethyl carbodenafil toxicity. J. Anal. Toxicol., 2017, 41(3), 250-255.
[PMID: 27999095]
[4]
Zou, P.; Hou, P.; Oh, S.S.Y.; Ge, X.; Bloodworth, B.C.; Low, M.Y.; Koh, H.L. Identification of benzamidenafil, a new class of phosphodiesterase-5 inhibitor, as an adulterant in a dietary supplement. J. Pharm. Biomed. Anal., 2008, 47(2), 255-259.
[http://dx.doi.org/10.1016/j.jpba.2008.01.004] [PMID: 18280079]
[5]
Kee, C.L.; Ge, X.; Gilard, V.; Malet-Martino, M.; Low, M.Y. A review of synthetic phosphodiesterase type 5 inhibitors (PDE-5i) found as adulterants in dietary supplements. J. Pharm. Biomed. Anal., 2018, 147, 250-277.
[http://dx.doi.org/10.1016/j.jpba.2017.07.031] [PMID: 28903860]
[6]
Hasegawa, T.; Takahashi, K.; Saijo, M.; Ishii, T.; Nagata, T.; Kurihara, M.; Haishima, Y.; Goda, Y.; Kawahara, N. Isolation and structural elucidation of cyclopentynafil and N-octylnortadalafil found in a dietary supplement. Chem. Pharm. Bull. (Tokyo), 2009, 57(2), 185-189.
[http://dx.doi.org/10.1248/cpb.57.185] [PMID: 19182409]
[7]
Venhuis, B.J.; Blok-Tip, L.; de Kaste, D. Designer drugs in herbal aphrodisiacs. Forensic Sci. Int., 2008, 177(2-3), e25-e27.
[http://dx.doi.org/10.1016/j.forsciint.2007.11.007] [PMID: 18178354]
[8]
Koh, H.L.; Woo, S.O. Chinese proprietary medicine in Singapore: regulatory control of toxic heavy metals and undeclared drugs. Drug Saf., 2000, 23(5), 351-362.
[http://dx.doi.org/10.2165/00002018-200023050-00001] [PMID: 11085343]
[9]
Ulloa, J.; Sambrotta, L.; Redko, F.; Mazza, O.N.; Garrido, G.; Becher, E.F.; Muschietti, L. Detection of a tadalafil analogue as an adulterant in a dietary supplement for erectile dysfunction. J. Sex. Med., 2015, 12(1), 152-157.
[http://dx.doi.org/10.1111/jsm.12759] [PMID: 25402198]
[10]
Shin, M.H.; Hong, M.K.; Kim, W.S.; Lee, Y.J.; Jeoung, Y.C. Identification of a new analogue of sildenafil added illegally to a functional food marketed for penile erectile dysfunction. Food Addit. Contam., 2003, 20(9), 793-796.
[http://dx.doi.org/10.1080/0265203031000121455] [PMID: 13129773]
[11]
Yeo, M.; Park, Y.; Lee, H.; Choe, S.; Baek, S.H.; Kim, H.K.; Pyo, J.S. New metabolites of hongdenafil, homosildenafil and hydroxyhomosildenafil. J. Pharm. Biomed. Anal., 2018, 149, 586-590.
[http://dx.doi.org/10.1016/j.jpba.2017.11.057] [PMID: 29197805]
[12]
Pyo, J.S. New metabolites of udenafil identified through liquid chromatography-quadrupole time-of-flight mass spectrometry. In: Curr. Pharm. Anal; 2021; 17, pp. (8)1000-1007.
[http://dx.doi.org/10.2174/1573412917666201208114954]
[13]
Coleman, M.D. Human Drug Metabolism: An Introduction, 2nd ed; Wiley: Hoboken, NA, 2010.
[http://dx.doi.org/10.1002/9780470689332]
[14]
Kafle, A.; Coy, S.L.; Wong, B.M.; Fornace, A.J., Jr; Glick, J.J.; Vouros, P. Understanding gas phase modifier interactions in rapid analysis by differential mobility-tandem mass spectrometry. J. Am. Soc. Mass Spectrom., 2014, 25(7), 1098-1113.
[http://dx.doi.org/10.1007/s13361-013-0808-5] [PMID: 24452298]

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