| Reference | [1]. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Feb 15;1139:121940. doi: 10.1016/j.jchromb.2019.121940. Epub 2019 Dec 13.<br />
Metabolic study of vardenafil analogues: Pseudovardenafil and hydroxyvardenafil.<br />
Heo D(1), Kang JS(1), Choe S(2), Lee S(3), Kim KM(4), Pyo J(5).<br />
Author information: (1)College of Pharmacy, Kyungsung University, Busan 48434, Republic of Korea. (2)Department of Drug and Toxicology, National Forensic Service, Wonju 26460, Republic of Korea. (3)College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 42601, Republic of Korea. (4)Department of Pharmaceutical Science and Technology, Kyungsung University, Busan 48434, Republic of Korea. (5)College of Pharmacy, Kyungsung University, Busan 48434, Republic of Korea. Electronic address: [email protected].<br />
Vardenafil, a remedy for erectile dysfunction, is easily modified, facilitating the creation of analogues that have been illegally added to functional foods and counterfeit medications. However, the medical profile of these analogues, including their safety, efficacy, safe drug combinations, metabolism and excretion, has not been completely evaluated, which could cause serious health problems. In this study, two representative vardenafil analogues, pseudovardenafil and hydroxyvardenafil, were metabolized with in-vitro model (human liver microsome) and in-vivo model (rats). The metabolized samples were extracted and characterized, using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS). Some imprecise interpretations were evaluated with tandem mass spectrometry (LC-Q-TOF-MS/MS) for mass fragmentation analysis. A total of 11 metabolites of pseudovardenafil and 13 metabolites of hydroxyvardenafil that were identified have never been reported. These new metabolites could be usefully applied to forensic science and other metabolic fields. Furthermore, they could serve as principal references for the toxicity, danger, and side effects of unlawful vardenafil counterfeits.<br />
DOI: 10.1016/j.jchromb.2019.121940 PMID: 31978742 [Indexed for MEDLINE]<br />
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[2]. J Pharm Biomed Anal. 2013 Feb 23;74:83-91. doi: 10.1016/j.jpba.2012.10.013. Epub 2012 Oct 22.<br />
Detection and structure elucidation of hydroxythiovardenafil as an adulterant in a herbal dietary supplement.<br />
Jankovics P(1), Lohner S, Darcsi A, Németh-Palotás J, Béni S.<br />
Author information: (1)National Institute of Pharmacy, Zrínyi u. 3., PO Box 450, H-1051 Budapest, Hungary. [email protected]<br />
A new derivative of vardenafil was detected in an alleged herbal dietary supplement and identified as 2-(2-ethoxy-5-(4-(2-hydroxyethyl)piperazin-1-ylsulfonyl)phenyl)-5-methyl-7-propyl-imidazo[1,5-f][1,2,4]triazin-4(3H)-thione. Structure elucidation was carried out by LC-UV-MS/MS and NMR. Results obtained with high resolution MS and IR spectroscopy confirmed the proposed chemical structure. The compound was distinguished from hydroxyvardenafil, a second active substance identified in the same product, by the conversion of the oxo group to a thio group on the imidazo-triazin moiety. Hydroxythiovardenafil was therefore suggested as a proprietary name for the new molecule. This is the first paper to describe a thio-analog of vardenafil in a commercially available product.<br />
DOI: 10.1016/j.jpba.2012.10.013 PMID: 23245238 [Indexed for MEDLINE]<br />
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[3]. J AOAC Int. 2008 May-Jun;91(3):580-8.<br />
Determination of analogs of sildenafil and vardenafil in foods by column liquid chromatography with a photodiode array detector, mass spectrometry, and nuclear magnetic resonance spectrometry.<br />
Choi DM(1), Park S, Yoon TH, Jeong HK, Pyo JS, Park J, Kim D, Kwon SW.<br />
Author information: (1)Korea Food and Drug Administration, 194 Tongilro, Eunpyeong-gu, Seoul 122704, Korea.<br />
Two analogs of sildenafil and vardenafil in food were detected by column liquid chromatography (LC) with a photodiode array detector. They were isolated by preparative LC; their structures were established by mass spectrometry and nuclear magnetic resonance spectrometry. One analog was found to be methisosildenafil (compound A), 5-(5-(3,5-dimethylpiperazin-1-ylsulfonyl)-2-ethoxy-phenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]-pyrimidin-7(6H)-one. It is a sildenafil analog with a dimethylpiperazine ring substituted for the methylpiperazine group. The second analog, hydroxyvardenafil (compound B) is reported for the first time in this study. Hydroxyvardenafil's International Union of Pure and Applied Chemistry name is 2-(2-ethoxy-5-(4-(2-hydroxyethyl)-piperazin-1-ylsulfonyl)phenyl)-5-methyl-7-propyl-imidazo[1,5-f][1,2,4]triazin-4(3H)-one. The novel vardenafil analog has a hydroxyl group added to the ethylpiperazine group.<br />
PMID: 18567304 [Indexed for MEDLINE]
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