Detection of 94 PDE-5is and Their Analogs Including N-Desmethylthiosildenafil in Various Formulations of Dietary Supplements and Food Samples Using HPLC and LC-Q-TOF/MS

• Published in: Journal of chromatographic science Vol. 60; no. 10; pp. 953 - 962
• Main Authors: Lee, Ji Hyun, Park, Ok Rim, Yang, Yoon Ji, Han, Ji Hye, Jung, Eun Ju, Kim, Nam Sook, Baek, Sun Young
• Format: Journal Article
• Language: English
• Published: United States 13.12.2022
• Subjects: Chromatography, High Pressure Liquid; Dietary Supplements - analysis; Drug Contamination; Humans; Phosphodiesterase 5 Inhibitors - analysis; Phosphodiesterase 5 Inhibitors - chemistry; Sildenafil Citrate - analysis; Tadalafil; Dietary supplement; High-performance liquid chromatography (HPLC); PDE-5 inhibitors; Food products; Illegal products; High-performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry (HPLC-Q-TOF/MS)
• ISSN: 0021-9665; 1945-239X
• DOI: 10.1093/chromsci/bmac015

Consumption of foods and dietary supplements (DS) adulterated with unprescribed or non-permitted phosphodiesterase-5 inhibitors (PDE-5i) and their analogs can cause serious risk to human health. This study aims to analyze 93 PDE-5i and their analogs present in adulterated foods and DS using an established and validated method involving high-performance liquid chromatography (HPLC). The method was validated in solid and liquid samples, resulting in a limit of detection and quantitation of 0.03-0.5 and 0.08-1.6 μg/mL, respectively. Using the validated method, a total of 404 samples were screened. It was found that 32% of 404 samples were illegally adulterated with PDE-5i and their analogs; moreover, 16.9% of the adulterated samples were found to contain more than three compounds. HPLC-quadrupole-time-of-flight (TOF)/mass spectrometry (MS) analysis was conducted on all the samples to confirm the detected compounds accurately based on fragmentation ion patterns. In addition, sildenafil and tadalafil were detected from the capsule shells of DS unusually. Subsequently, the detected compounds were identified and quantified using HPLC at concentrations ranging from 0.007 to 370.0 mg/g. NMR analysis was carried out to confirm the accurate chemical structure of a compound found during the TOF/MS analysis, which did not match with the 93 reference standards.; it was identified to be N-desmethylthiosildenafil. In this study, various PDE-5i compounds and their analogs were detected from low to high concentrations in a sample. Therefore, the study sheds light on the misuse of PDE-5i and their analogs in consumable products, which pose a severe threat to public health.