Kee Chee-Leong, Ge Xiaowei, Low Min-Yong, Gilard Véronique, Malet-Martino Myriam
Pharmaceutical Laboratory, Applied Sciences Group, Health Sciences Authority, Singapore.
Laboratoire IMRCP (UMR CNRS 5623), Université Paul Sabatier, Université de Toulouse, Toulouse cedex, France.
Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2023 Dec;40(12):1495-1530. doi: 10.1080/19440049.2023.2279567. Epub 2023 Dec 13.
This article is an up-to-date review of 112 unapproved phosphodiesterase type 5 inhibitors (PDE-5i) found as adulterants in sexual enhancement dietary supplements and other products from 2003 to July 2023. Seventy-five of these unapproved PDE-5i are analogues of sildenafil (67%), followed by 26 analogues of tadalafil (23%), 9 analogues of vardenafil (8%) and 2 other type of compounds (2%). The products have been formulated in various packaging, primarily in capsule, tablet, and powder forms. Common screening techniques allowing detection of such analogues include high performance or ultra-high performance liquid chromatography in tandem with ultra-violet detector (HPLC-UV or UPLC-UV) (50%) and thin-layer chromatography in tandem with ultra-violet detection (TLC-UV) (7%). Screening by mass spectrometry (MS) is relatively less common with the use of single-, triple-quadrupole or time-of-flight (TOF) mass spectrometers (9%). Meanwhile, the combined detection by UV-MS has been recorded at 10% usage. Screening by proton nuclear magnetic resonance spectroscopy (NMR) (11%) has also been applied. For compound characterization, i.e. structural elucidation, NMR spectroscopy has been preferred (100 out of 112 compounds), followed by high-resolution mass spectrometry (HRMS) (74 out of 112 compounds) and Fourier-transform infrared spectroscopy (FTIR) (44 out of 112 compounds). Over the past two decades, analytical technology has been evolving with enhanced sensitivity and resolution. Despite this, structural elucidation of the new emerging analogues in adulterated dietary supplements remains a challenge, especially when the analogues involve complex structural modification. Therefore, the above-mentioned techniques may not be adequate to characterize the analogues. Additional work involving chiroptical methods, two-dimensional (2D) NMR experiments and X-ray crystallography are likely to be required in the future.
本文是一篇最新综述，介绍了2003年至2023年7月期间在性增强膳食补充剂和其他产品中作为掺假物被发现的112种未经批准的5型磷酸二酯酶抑制剂（PDE-5i）。这些未经批准的PDE-5i中，75种是西地那非类似物（67%），其次是26种他达拉非类似物（23%），9种伐地那非类似物（8%）和2种其他类型的化合物（2%）。这些产品有多种包装形式，主要是胶囊、片剂和粉末形式。能够检测此类类似物的常见筛选技术包括高效液相色谱或超高效液相色谱串联紫外检测器（HPLC-UV或UPLC-UV）（50%）和薄层色谱串联紫外检测（TLC-UV）（7%）。使用单四极杆、三重四极杆或飞行时间（TOF）质谱仪进行质谱（MS）筛选相对较少（9%）。同时，紫外-质谱联用检测的使用记录为10%。也应用了质子核磁共振波谱（NMR）筛选（11%）。对于化合物表征，即结构解析，核磁共振波谱是首选方法（112种化合物中有100种），其次是高分辨率质谱（HRMS）（112种化合物中有74种）和傅里叶变换红外光谱（FTIR）（112种化合物中有44种）。在过去二十年中，分析技术不断发展，灵敏度和分辨率不断提高。尽管如此，掺假膳食补充剂中新出现的类似物的结构解析仍然是一项挑战，尤其是当类似物涉及复杂的结构修饰时。因此，上述技术可能不足以对类似物进行表征。未来可能需要开展涉及旋光方法、二维（2D）核磁共振实验和X射线晶体学的额外工作。
