title: Simultaneous Measurement of Serum Chemical Castration Agents and Testosterone Levels Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.
abstract: Chemical castration involves administration of drugs to prevent pathological sexual behavior, reduce abnormal sexual drive and treat hormone-dependent cancers. Various drugs have been used for chemical castration; however, substantial interindividual variability and side effects are often observed. In this study, we proposed a useful monitoring method for the application of chemical castration agents using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Testosterone, cyproterone acetate, medroxyprogesterone, goserelin acetate, leuprolide acetate and triptorelin acetate were analyzed by UPLC-MS-MS. The target drugs were extracted from serum samples by double protein precipitation using methanol. Testosterone-1,2-d2 and buserelin acetate were used as internal standards. Parameters of analytical performance were evaluated, including imprecision, linearity, ion suppression and detection capabilities. Testosterone measurements were compared with the results of immunoassays. Serum specimens from 51 subjects who underwent chemical castration were analyzed. All drugs and testosterone were well extracted and separated using our method. The method was essentially free from potential interferences and ion suppression. Within-run and between-run imprecision values were <15%. The lower limits of quantification were 0.125 and 0.5-1.0 ng/mL for testosterone and other drugs, respectively. Good correlations with pre-existing immunoassays for testosterone measurement were observed. Sera from subjects who underwent androgen deprivation therapy showed variable levels of drugs. We successfully developed a UPLC-MS-MS-based monitoring method for chemical castration. The performance of our method was generally acceptable. This method may provide a novel monitoring strategy for chemical castration to enhance expected effects while reducing unwanted side effects.
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Ko
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Kyunghoon
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Jeon
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Yeo-Min
authors.initials: YM
authors.lastname: Yun
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Sail
authors.initials: S
authors.lastname: Chun
authors.affiliation: Forensic Science Division II, Supreme Prosecutors' Office, Seoul, Korea.
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Forensic Science Division II, Supreme Prosecutors' Office, Seoul, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Forensic Science Division II, Supreme Prosecutors' Office, Seoul, Korea.
authors.forename: Moon Kyo
authors.initials: MK
authors.lastname: In
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea songjhcp@snu.ac.kr.
authors.forename: Junghan
authors.initials: J
authors.lastname: Song
mesh_terms: D000328:Adult; D059002:Androgen Receptor Antagonists / Q000097:blood*; D002138:Calibration; D002369:Castration; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D057230:Limit of Detection; D008297:Male; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000097:blood*
chemical_list: D059002:Androgen Receptor Antagonists; D013739:Testosterone