Analysis of phosphodiesterase type 5 inhibitors and analogues as adulterants in herbal dietary food supplements in Saudi market using green UPLC-MS/MS method: Assessment of the greenness and whiteness profiles

Abstract

Herbal dietary supplements are popular alternatives to oral phosphodiesterase type 5 inhibitors (PDE5Is) for treating Erectile Dysfunction (ED), yet concerns arise regarding their adulteration with undeclared synthetic PDE5Is or analogues, posing health risks. The aim of this study was to develop and validate a green UPLC-MS/MS method for sensitive and rapid detection of PDE5Is and analogues in sexual enhancement herbal dietary supplements marketed in Saudi Arabia. Method validation revealed good linearity with determination coefficients (r2) ≥ 0.9990, and LODs and LOQs in the range of 0.4 – 32 ng g−1 and 1––96 ng g−1, respectively. The accuracy ranged from 80.8 % to 103.4 % while inter-day precision was ≤ 8.6 % and intra-day precision was ≤ 8.4 %. The method was successfully utilized to analyze 32 herbal dietary supplements. The results revealed that 18 samples (56.3 %) tested positive for at least one of the target analytes. Sildenafil emerged as the most frequently detected analyte, found in 15 samples (20.1 µg g−1 to 37,492 µg g−1). Tadalafil was detected in 7 samples, with concentrations ranging from 4.46 µg g−1 to 19,986 µg g−1. Yohimbine was detected in only 4 samples, while icariin was detected at lower concentrations in 3 samples. Furthermore, the method greenness and whiteness profiles were evaluated using four metrics including the Analytical Eco-Scale, Green Analytical Procedure Index (GAPI), Analytical GREEnness (AGREE) metric, and Red-Green-Blue 12 (RGB 12) metric.This study provides foundational data on the adulteration of dietary supplements in Saudi Arabia and offers insights for future interventions to promote consumer safety and awareness regarding herbal dietary supplement consumption.