Main Article Content
Sildenafil, tadalafil, and vardenafil are phosphodiesterase type 5 enzyme (PDE-5) inhibitors used for the treatment of male erectile dysfunction. This present study aims to investigate 55 herbal products indicated for men’s sexual health from the Malaysian market for adulteration of PDE-5 inhibitors and analogues. The screening and identification of 20 PDE-5 inhibitors and analogues in herbal products of various forms (powder, capsules, tablets, and pastels) were conducted using gas chromatography–electron impact-mass spectrometer (GC-EI-MS). The analysis has shown that 19 herbal products were adulterated with PDE-5 inhibitors and analogues. Unique ion fragmentations and the presence of molecular ion serve as potential markers, and the limit of detection (LOD) was 0.1-5.0 µg/g. Ten PDE-5 inhibitors and analogues were randomly selected and successfully validated for simultaneous quantification, whereby the limit of quantitation (LOQ) was 5.0–50.0 µg/g with recoveries at 86.1-118.9%. The developed method of GC-EI-MS was shown to be simple, throughput, economical and had sufficient sensitivity to screen, identify and quantify PDE-5 inhibitors and analogues in herbal matrices.
Received 20/10/2019, Accepted 1/4/2020, Published 1/12/2020
This work is licensed under a Creative Commons Attribution 4.0 International License.
Damiano F, Silva C, Gregori A, Vacondio F, Mor M, Menozzi M, et al. Analysis of illicit dietary supplements sold in the Italian market: Identification of a sildenafil thio-derivative as adulterant using UPLC-TOF/MS and GC/MS. Sci Justice. 2014;54:228–37.
Vaclavik L, Krynitsky AJ, Rader JI. Mass spectrometric analysis of pharmaceutical adulterants in products labelled as botanical dietary supplements or herbal remedies: A review. Anal Bioanal Chem. 2014;406:6767-90.
ElAgouri G, AlAmrawy F, ElYazbi A, Eshra A, Nounou MI. Male enhancement nutraceuticals in the middle east market: Claim, pharmaceutical quality and safety assessments. Int J Pharm. 2015 Aug; 492:109-19.
Rocha T, Amaral JS, Oliveira MBPP. Adulteration of dietary supplements by the illegal addition of synthetic drugs: A review. Compr Rev Food Sci Food Saf. 2015;15:43-62.
Bujang NB, Chee CF, Heh CH, Rahman NA, Buckle MJC. Phosphodiesterase-5 inhibitors and their analogues as adulterants of herbal and food products: analysis of the Malaysian market, 2014-16. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2017; 34(7):1101-9.
Viigimaa M, Vlachopoulos C, Lazaridis A, Doumas M. Management of erectile dysfunction in hypertension: Tips and tricks. World J Cardiol. 2014 ; 6(9):908–15.
Campbell N, Clark JP, Stecher VJ, Thomas JW, Callanan AC, Donnelly BF, et al. Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type-5 inhibitors. J Sex Med. 2015;10:1842-9.
Lin YT, Huang YC, Lee HC, Liao CH, Lin YL, Tsai CF, et al. Isolation and identification of a novel sildenafil analogue adulterant in herbal products. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2017;34(3):330-4.
Huang Y-C, Lee H-C, Lin Y-L, Lin Y-T, Tsai C-F, Cheng H-F. Identification of a new sildenafil analogue adulterant, desethylcarbodenafil, in a herbal supplement. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2016;33(11)1637-42.
Ulloa J, Sambrotta L, Redko F, Mazza ON, Garrido G, Becher EF, et al. Detection of a tadalafil analogue as an adulterant in a dietary supplement for erectile dysfunction. J Sex Med. 2015;12:152-7.
Balayssac S, Gilard V, Zedde C, Martino R, Malet-Martino M. Analysis of herbal dietary supplements for sexual performance enhancement: First characterisation of propoxyphenyl-thiohydroxyhomosildenafil and identification of sildenafil, thiosildenafil, phentolamine and tetrahydropalmatine as adulterants. J Pharm Biomed Anal. 2012; 63:135-50.
Lee ES, Lee JH, Han KM, Kim JW, Hwang IS, Cho S, et al. Simultaneous determination of 38 phosphodiesterase-5 inhibitors in illicit erectile dysfunction products by liquid chromatography-electrospray ionisation-tandem mass spectrometry. J Pharm Biomed Anal. 2013; 83:171-8.
Lin YT, Huang YC, Lee HC, Liao CH, Lin YL, Tsai CF, et al. Isolation and identification of a novel sildenafil analogue adulterant in herbal products. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2017;34(3):330–4.
Wollein U, Eisenreich W, Schramek N. Identification of novel sildenafil-analogues in an adulterated herbal food supplement. J Pharm Biomed Anal. 2011;56(4):705-12.
Patel DN, Li L, Kee CL, Ge X, Low MY, Koh HL. Screening of synthetic PDE-5 inhibitors and their analogues as adulterants: Analytical techniques and challenges. J Pharm Biomed Anal. 2014;87:176-90.
Lee JH, Park HN, Park OR, Kim NS, Park SK, Kang H. Screening of illegal sexual enhancement supplements and counterfeit drugs sold in the online and offline markets between 2014 and 2017. Forensic Sci. 2019;298:10-19.
Guo JB, Xu Y, Huang ZB, He QH, Liu SW. Development of an immunoassay for rapid screening of vardenafil and its potential analogues in herbal products based on a group-specific monoclonal antibody. Anal Chim Acta. 2010;658(2):197-203.
Cai Y, Cai TG, Shi Y, Cheng XL, Ma LY, Ma SC, et al. Simultaneous determination of eight PDE5-is potentially adulterated in herbal dietary supplements with TLC and HPLC-PDA-MS methods. Chromatogr Relat Technol. 2010;33(13):1287-306.