Reliable screening and classification of phosphodiesterase type 5 inhibitors in dietary supplements using gas chromatography / mass spectrometry combined with specific common ions

• Published in: Journal of Chromatography A 2020-07, Vol.1623, p.461210, Article 461210
• Main Authors: Lee, Wonwoong, Kim, Hyun Ji, Lee, Myung Eun, Kim, Beom Hee, Park, Seongchul, Lee, Ji Hyun, Lee, Yong-Moon, Oh, Han Bin, Hong, Jongki
• Format: Article
• Language: English
• Subjects: Dietary supplements; EI mass fragmentations; Extracted common ion chromatogram; GC-MS; Phosphodiesterase type 5 inhibitors; Trimethylsilylation
• ISSN: 0021-9673
• DOI: 10.1016/j.chroma.2020.461210

•Development of a GC–MS method to screen 53 PDE-5i drugs in dietary supplements.•Microscale sample preparation combined with simple LLE and trimethylsilylation.•First description of characteristic common EI fragment ions of PDE-5i TMS derivatives.•Construction of ECICs and discriminant analysis (DA) based on specific common ions.•Reliable screening and classification of PDE-5i in supplements using ECICs and DA. Illegal dietary supplements adulterated with phosphodiesterase type 5 inhibitors (PDE-5i) are increasingly widely distributed through internet markets and underground routes. For this reason, it demands development of reliable screening methods to determine a wide range of PDE-5i drugs in various types of dietary supplements. Herein, we developed a screening method using gas chromatography-mass spectrometry (GC–MS) for simultaneous detection of 53 PDE-5i drugs in supplements. Common formulations (such as capsule, powder, pill, and tablet) of supplements with complicated matrices were treated by simple liquid–liquid extraction and trimethylsilyl (TMS) derivatization. With the aid of TMS derivatization, 53 PDE-5i drugs could be successfully separated and detected within 15 min, using a short microbore GC column (15 m). Moreover, owing to enhanced detection sensitivity and selectivity of PDE-5i TMS derivatives, 0.5 mg of sample was sufficient to screen and confirm targeted PDE-5i drugs. In this study, specific common ions according to structural characteristics of PDE-5i drugs were found under the electron ionization (EI) of their TMS derivatives. These specific common fragments could reflect the common pharmacophores for 4 classes of PDE-5i drugs (sildenafil, other sildenafil, vardenafil, and tadalafil analogues). Based on characteristic EI fragment ions, extracted common ion chromatograms (ECICs) and discriminant analysis (DA) were effectively used for reliable screening and classification of various types of PDE-5i drugs. Specific ECICs and DA using characteristic EI fragments here will aid in identification of newly emerging PDE-5i counterfeits in supplements. This study will be helpful to supervise illegal adulteration of PDE-5i drugs in dietary supplements to protect public health and consumer safety.