An LC-MS/MS method for the determination of five erectile dysfunction drugs and their selected metabolites in hair.
The abuse of sildenafil and its analogous, accelerated by their inappropriate or illegal distribution, is a serious social issue globally. However, no studies have been conducted to monitor these drugs simultaneously in hair, which can provide valuable information on chronic drug use. In the present study, an LC-MS/MS method was developed for the simultaneous determination in hair of five erectile dysfunction drugs having a high risk for abuse (mirodenafil, sildenafil, tadalafil, udenafil and vardenafil) and their selected metabolites (SK3541, desmethylsildenafil, DA8164 and desethylvardenafil). The novel method was fully validated after optimizing matrix effects and extraction efficiency. The optimized sample preparation included acidic methanol extraction followed by solid phase extraction using C18 mixed mode strong cation exchange polymeric cartridges. The prepared samples were analyzed by LC-MS/MS with electrospray ion source in the positive ionization mode. The validation results proved the method to be selective, sensitive, accurate and precise, with acceptable linearity within calibration ranges. LODs ranged from 0.05 (DA8164) to 1 ng/10 mg hair (tadalafil). LOQs were 1 ng/10 mg hair except for DA8164 and vardenafil, of which they were 2.5 ng/10 mg hair. No significant variations were observed by different sources of matrices in both human and rat hair, except for tadalafil, for which a stable isotope-labeled internal standard was effective. The animal study suggested hair pigmentation was a major factor for the incorporation of the drugs and metabolites into hair. However, a wide variation of the sildenafil-to-desmethylsildenafil ratios was observed in human hair samples. The developed method will be very useful for monitoring the abuse of erectile dysfunction drugs for both legal and public health aspects.
['Lee|Sooyeun|S|', 'Choi|Boyeon|B|', 'Kim|Jihyun|J|', 'In|Sanghwan|S|', 'Baeck|Seungkyung|S|', 'Oh|Seung Min|SM|', 'Chung|Kyu Hyuck|KH|']
D000818:Animals D002853:Chromatography, Liquid D007172:Erectile Dysfunction D006197:Hair D006801:Humans D057230:Limit of Detection D016014:Linear Models D008297:Male D058986:Phosphodiesterase 5 Inhibitors D010879:Piperazines D051381:Rats D011924:Rats, Zucker D015203:Reproducibility of Results D013449:Sulfonamides D053719:Tandem Mass Spectrometry D064804:Urological Agents
Erectile dysfunction drugs Matrix effects Hair pigmentation Drug abuse Hair analysis Liquid chromatography–tandem mass spectrometry