Santillo Michael F, Mapa Mapa S T
Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, Maryland, USA.
Drug Test Anal. 2018 Feb 28. doi: 10.1002/dta.2375.
Products marketed as dietary supplements for sexual enhancement are frequently adulterated with phosphodiesterase-5 (PDE5) inhibitors, which are erectile dysfunction drugs or their analogs that can cause adverse health effects. Due to widespread adulteration, a rapid screening assay was developed to detect PDE5 inhibitors in adulterated products. The assay employs fluorescence detection and is based on measuring inhibition of PDE5 activity, the pharmacological mechanism shared among the adulterants. Initially, the assay reaction scheme was established and characterized, followed by analysis of 9 representative PDE5 inhibitors (IC , 0.4-4.0 ng mL ), demonstrating sensitive detection in matrix-free solutions. Next, dietary supplements serving as matrix blanks (n = 25) were analyzed to determine matrix interference and establish a threshold value; there were no false positives. Finally, matrix blanks were spiked with 9 individual PDE5 inhibitors, along with several mixtures. All 9 adulterants were successfully detected (≤ 5 % false negative rate; n = 20) at a concentration of 1.00 mg g , which is over 5 times lower than concentrations commonly encountered in adulterated products. A major distinction of the PDE5 inhibition assay is the ability to detect adulterants without prior knowledge of their chemical structures, demonstrating a broad-based detection capability that can address a continuously evolving threat of new adulterants. The PDE5 inhibition assay can analyze over 40 samples simultaneously within 15 minutes and involves a single incubation step and simple data analysis, all of which are advantageous for combating the widespread adulteration of sex-enhancement products.
作为性增强膳食补充剂销售的产品经常被掺假，含有磷酸二酯酶-5（PDE5）抑制剂，这些是勃起功能障碍药物或其类似物，可能会对健康产生不良影响。由于掺假现象普遍，因此开发了一种快速筛查方法来检测掺假产品中的PDE5抑制剂。该方法采用荧光检测，基于测量PDE5活性的抑制作用，这是掺假物共有的药理机制。最初，建立并表征了检测反应方案，随后分析了9种代表性PDE5抑制剂（IC，0.4 - 4.0 ng mL），证明在无基质溶液中检测灵敏。接下来，分析了作为基质空白的膳食补充剂（n = 25）以确定基质干扰并建立阈值；没有假阳性。最后，向基质空白中加入9种单独的PDE5抑制剂以及几种混合物。所有9种掺假物在浓度为1.00 mg g时均成功检测到（假阴性率≤5%；n = 20），该浓度比掺假产品中常见浓度低5倍以上。PDE5抑制测定法的一个主要区别在于能够在不预先了解掺假物化学结构的情况下检测掺假物，展示了一种广泛的检测能力，可应对不断演变的新掺假物威胁。PDE5抑制测定法可在15分钟内同时分析40多个样品，且只需一个孵育步骤和简单的数据分析，所有这些对于打击性增强产品的广泛掺假都具有优势。
