| Reference | [1]. J Pharm Biomed Anal. 2016 Sep 5;128:360-366. doi: 10.1016/j.jpba.2016.05.038. Epub 2016 May 27.<br />
Isolation and structural characterization of a new tadalafil analog (chloropropanoylpretadalafil) found in a dietary supplement.<br />
Kern SE(1), Lorenz LM(2), Lanzarotta A(2), Nickum EA(2), Litzau JJ(2).<br />
Author information: (1)U.S. Food and Drug Administration, Forensic Chemistry Center, Cincinnati, OH, United States. Electronic address: [email protected]. (2)U.S. Food and Drug Administration, Forensic Chemistry Center, Cincinnati, OH, United States.<br />
A screen for known PDE-5 inhibitors in a dietary supplement product marketed for "enhanced sexual performance" detected a compound that structurally resembled chloropretadalafil, a known analog of tadalafil. The compound was isolated from the supplement matrix using high performance liquid chromatography with ultraviolet detection (HPLC-UV) and a fraction collector, and was further characterized using gas chromatography with Fourier Transform infrared detection and mass spectral detection (GC/FT-IR/MS), as well as high resolution mass spectrometry (HRMS). The analog had an accurate mass of m/z 441.1216 (error is 0.8706ppm) for the protonated species [M+H](+), corresponding to a molecular formula of C23H22ClN2O5. HRAM and GC/FT-IR/MS mass spectral fragmentation data suggested that the modification is a chloropropanoyl moiety extending from the nitrogen on the piperidine ring of chloropretadalafil. The proposed new analog has been named chloropropanoylpretadalafil.<br />
DOI: 10.1016/j.jpba.2016.05.038 PMID: 27337189 [Indexed for MEDLINE]<br />
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[2]. Kern, S.E., Lorenz, L.M., Lanzarotta, A., Nickum, E.A. and Litzau, J.J., 2015.<br />
Isolation and structural characterization of a new tadalafil analog (chloropropanoylpretadalafil) found in a dietary supplement.<br />
Abstract: A screen for known PDE-5 inhibitors in a dietary supplement product marketed for “enhanced sexual performance” detected a compound that structurally resembled chloropretadalafil, a known analog of tadalafil. The compound was isolated from the supplement matrix using high performance liquid chromatography with ultraviolet detection (HPLC-UV) and a fraction collector, and was further characterized using gas chromatography with Fourier Transform infrared detection and mass spectral detection (GC/FT-IR/MS), as well as high resolution mass spectrometry (HRMS). The analog had an accurate mass of m/z 441.1216 (error is 0.8706 ppm) for the protonated species [M+H]+, corresponding to a molecular formula of C23H22ClN2O5. HRAM and GC/FT-IR/MS mass spectral fragmentation data suggested that the modification is a chloropropanoyl moiety extending from the nitrogen on the piperidine ring of chloropretadalafil. The proposed new analog has been named chloropropanoylpretadalafil.<br />
Journal of pharmaceutical and biomedical analysis, 103, p.99.<br />
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[3]. Lee, E.S., Lee, J.H., Han, K.M., Kim, J.W., Hwang, I.S., Cho, S., Han, S.Y. and Kim, J., 2013.<br />
Simultaneous determination of 38 phosphodiestrase-5 inhibitors in illicit erectile dysfunction products by liquid chromatography–electrospray ionization-tandem mass spectrometry.<br />
Abstract: This paper describes the development and validation of simultaneous analytical method for 38 compounds, sildenafil, tadalafil, vardenafil and their analogues in illicit erectile dysfunction (ED) products by the liquid chromatography–electrospray ionization-tandem mass method (LC–ESI-MS/MS). Chromatographic separation was performed on a C18 reversed-phase column using a gradient of solvent A: aqueous 2 mM ammonium formate solution and solvent B: acetonitrile (ACN). All components were monitored under time-scheduled multiple reaction monitoring (MRM) mode. The limits of detection (LOD) ranged from 0.004 ng/ml to 0.455 ng/ml and the limits of quantification (LOQ) ranged from 0.012 ng/ml to 1.5 ng/ml. Calibration curves were linear with correlation coefficients over 0.9991. Mean recoveries ranged from 73.6% to 111.3%, and relative standard deviation (RSD) was less than 10%. The intra- and inter-day precision ranged from 0.2% to 16.3% and from 0.2% to 17.0%, respectively. The proposed method was applied to investigate the 52 illicit ED products.<br />
Journal of pharmaceutical and biomedical analysis, 83, pp.171-178.<br />
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[4]. Lee, J.H., Min, A.Y., Park, O.R., Han, J.H., Yang, Y.J., Kim, H. and Baek, S.Y., 2021.<br />
Detection of 94 compounds related to sexual enhancement including sildenafil, tadalafil, vardenafil and their analogues in various formulations of dietary supplements and food samples using HPLC and LC-MS/MS.<br />
ABSTRACT: With an increase in the detection of structural and functional analogues of phosphodiesterase type 5 inhibitors (PDE-5i) in dietary supplements (DS) and foods, public health is threatened. Some products advertise natural ingredients despite containing PDE-5i that can cause serious adverse effects on human health. To avoid detection during routine screening, novel PDE-5i have been synthesised and added to DS and foods. The purpose of this study was to detect, identify, and quantify 94 PDE-5i and related compounds in DS and foods. Furthermore, the study investigated the detection cases and compared them by sample type, formulation, and compounds. The HPLC and LC-MS/MS methods were validated for limit of detection (LOD), limit of quantification (LOQ), linearity, and recovery in solid and liquid type samples. Both HPLC and LC-MS/MS showed satisfactory results, which were in conformance with the ICH guidelines. A total of 404 samples, including DS (99), and foods (305) were purchased from online and offline markets. Samples divided into 5 types of formulation were analysed; tablet, capsule, pilula (herbal medicine pill), powder and liquid type. Of these 130 samples (47 of 99 DS, and 83 of 305 foods) contained one or more PDE-5i or related compounds. Among the five types of formulation, the tablet type showed the highest detection rate (61.1%) in DS, whereas the capsule type showed the highest detection rate (53.8%) in food samples. This study will be helpful for monitoring illegal ED-related products, providing information to consumers, and ultimately contributing to protecting public health.<br />
Food Additives & Contaminants: Part A, 38(5), pp.769-781.<br />
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[5]. Lee, E.S., Kim, J.W., Lee, J.H., Han, K.M., Cho, S., Hwang, I., Han, S.Y., Chae, K. and Kim, J., 2013.<br />
Identification of a new tadalafil analogue found in a dietary supplement.<br />
Abstract: A new tadalafil analogue, acetaminotadalafil, was detected by HPLC in a bulk powder that is being used as an ingredient formanufacturing dietary supplements. The analogue was isolated by semi-preparative HPLC. A chemical structure of the new compound was elucidated by HPLC, LC-quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS), nuclear magnetic resonance (NMR), infrared (IR) and circular dichroism (CD) spectroscopy. The compound was identified as an acetylatedcompound of aminotadalafil. The structure of the previous unknown compound was confirmed as (6R,12aR)-2-acetamino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-pyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione and named as acetaminotadalafil.<br />
Food Additives & Contaminants: Part A, 30(4), pp.621-626.
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