Simultaneous Determination of Synthetic Phosphodiesterase-5 Inhibitors in Dietary Supplements by Liquid Chromatography-High Resolution/Mass Spectrometry

Abstract

After success of sildenafil for the treatment of erectile dysfunction, a large number of its analogues have been approved from FDA. Recently, the illegal dietary supplements which include sildenafil, vardenafil, tadalafil, or analogues of these drugs as ingredient have been widely distributed. Therefore, the determination of the residue of synthetic phosphodiesterase-5 (PDE-5) inhibitors in dietary supplements is highly required due to indiscriminate and unintentional overdose caused nausea, chest pains, fainting and irregular heartbeat. In this paper, we report a rapid and sensitive analytical method for the simultaneous determination of nine phosphodiesterase-5 inhibitors by liquid chromatography-high resolution mass spectrometry. The present method was found to be accurate and reproducible with 40 µg/g of the limit of quantification for the nine PDE-5 inhibitors. The developed method can be successfully applied to the analysis of the seven illegal dietary supplements.

Screening of Phosphodiesterase-5 Inhibitors and Their Analogs in Dietary Supplements by Liquid Chromatography–Hybrid Ion Trap–Time of Flight Mass Spectrometry

“…The retention times and mass errors of all analytes are listed in Table 1, and the extracted ion chromatograms are depicted in Figure 1. (6), piperidinohongdenafil (7), homosildenafil (8), dimethylsildenafil (9), udenafil (10), cyclopentinafil (11), thiosildenafil (12), hydroxythiohomosildenafil (13), thiohomosildenafil (14), dimethylthiosildenafil (15), oxohongdenafil (16), benzylsildenafil (17), hydroxychlorodenafil (18), chlorodenafil (19), nitrodenafil (20), nor-neosildenafil (21), dichlorodenafil (22), vardenafil (23), acetylvardenafil (24), hydroxyvardenafil (25), nor-neovardenafil (26), desulfovardenafil (27), pseudovardenafil (28), tadalafil (29), aminotadalafil (30), acetaminotadalafil (31), demethyltadalafil (32), chloropretadalafil (33), N-octyltadalafil (34), yohimbine (35), mirodenafil (36), thioquinapiperifil (37), xanthoanthrafil (38), and phenolphthalein (39). * indicated the analytes among multiple peaks in the EIC.…”

“…Thus, herbal therapies have successfully captured the market because most people believe that they are safe from adverse effects, and they can be purchased without any prescription [3][4][5]. However, taking advantage of the recognition that natural products are safe, illegally adding synthetic PDE-5 inhibitors and their analogs to herbal dietary supplements or making counterfeit drugs began to be distributed [6][7][8][9][10][11][12]. Since the detection of the first sildenafil analog, homosildenafil, in dietary supplements, the number of analogs has steadily increased owing to various structural modifications of the original drugs [5,6].…”

“…Further, QqQ MS can only be used for the quantitative analysis of known compounds and not for screening purposes. Therefore, other spectroscopic methods such as high-resolution mass spectrometry (HRMS) based on Fourier transform ion cyclotron resonance (FT-ICR) [ 31 ], time of flight (TOF) [ 24 , 25 , 28 , 29 , 33 ], orbitrap [ 8 , 12 , 26 , 27 ], and nuclear magnetic resonance spectrometry [ 4 , 6 , 7 , 9 , 30 , 34 , 35 , 36 , 37 , 38 ] must be applied to clarify the structure of the analytes. In particular, hybrid ion trap (IT)–HRMS, including IT–TOF and Orbitraps (LTQ–Orbitrap and Orbitrap Fusions), is one of the most effective tools for screening and identification of unknown compounds owing to its high-resolution and multistage tandem MS (MS n ) ability.…”

Simultaneous determination of 38 phosphodiestrase-5 inhibitors in illicit erectile dysfunction products by liquid chromatography–electrospray ionization-tandem mass spectrometry

“…Additionally, ammonium formate and acetic acid (with formic acid or not) were selected as a solvent modifier [3,14,15,21,22]. According to previous research, MeOH was not good for separation between sildenafil and vardenafil [14,20], and formic acid was not suitable for analysis of the compounds having amino groups such as sildenafil, homosildenafil, and hydroxyhomosildenafil [18].…”

“…ACN and MeOH have been widely used as organic solvent in PDE-5 inhibitors analysis using LCMS and LC-MS/MS [3,[13][14][15]21]. Additionally, ammonium formate and acetic acid (with formic acid or not) were selected as a solvent modifier [3,14,15,21,22].…”