title: An LC-MS/MS method for the determination of five erectile dysfunction drugs and their selected metabolites in hair.
abstract: 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.
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701, Republic of Korea.
authors.forename: Sooyeun
authors.initials: S
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701, Republic of Korea.
authors.forename: Boyeon
authors.initials: B
authors.lastname: Choi
authors.affiliation: National Forensic Service, 10 Ipchoon-ro, Wonju, Kangwon-do 220-170, Republic of Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: National Forensic Service, 10 Ipchoon-ro, Wonju, Kangwon-do 220-170, Republic of Korea.
authors.forename: Sanghwan
authors.initials: S
authors.lastname: In
authors.affiliation: National Forensic Service, 10 Ipchoon-ro, Wonju, Kangwon-do 220-170, Republic of Korea.
authors.forename: Seungkyung
authors.initials: S
authors.lastname: Baeck
authors.affiliation: Hoseo Toxicology Research Center, Hoseo University, 20 Hoseo-ro, 79 beon-gil, Asan, Chungcheongnam-do 336-795, Republic of Korea.
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Oh
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea. Electronic address: khchung@skku.edu.
authors.forename: Kyu Hyuck
authors.initials: KH
authors.lastname: Chung
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006197:Hair / Q000737:chemistry*; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000032:analysis* / Q000627:therapeutic use; D010879:Piperazines / Q000032:analysis / Q000627:therapeutic use; D051381:Rats; D011924:Rats, Zucker; D015203:Reproducibility of Results; D013449:Sulfonamides / Q000032:analysis / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry / Q000379:methods*; D064804:Urological Agents / Q000032:analysis* / Q000627:therapeutic use
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D013449:Sulfonamides; D064804:Urological Agents
keywords: Drug abuse; Erectile dysfunction drugs; Hair analysis; Hair pigmentation; Liquid chromatography–tandem mass spectrometry; Matrix effects