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Quantitative LC–MS/MS method in urine for the detection of drugs used to reverse the effects of chemical castration

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Abstract

The chemical castration law, which targets child molesters with recidivism, was introduced in Korea in 2011. For this, leuprolide, a gonadotropin-releasing hormone agonist, is used to decrease testosterone production and suppress libido. In order to achieve efficient law enforcement, it is necessary to monitor intentional ingestion of drugs that antagonize the effect of leuprolide. Therefore, an analytical method for the simultaneous detection of mirodenafil, sildenafil, tadalafil, udenafil, vardenafil, icariin, alprostadil, and yohimbine, which are the major impotence treatment drugs, legitimately or otherwise, in Korea, as well as their selected metabolites, in human urine was established and validated using liquid chromatography–tandem mass spectrometry (LC–MS/MS). First, different sample preparation methods, two solid-phase extractions with different cartridges and protein precipitation, were compared and protein precipitation was chosen for the entire study because it showed better matrix effects and recoveries. Thus, the drugs and metabolites in urine were extracted by protein precipitation and then filtered and analyzed by LC–MS/MS with polarity switching electrospray ionization. The validation results of selectivity, matrix effect, recovery, linearity, intra- and inter-assay precision and accuracy were satisfactory. The limits of detection ranged from 0.25 to 10 ng/mL, and the limits of quantification were 2.5 to 50 ng/mL. The drugs and metabolites in urine did not show any degradation under storage for 7 and 15 days at 4 and −20 °C as well as after three freeze–thaw cycles. The developed method will be very useful for monitoring the illegal use of impotence treatment drugs.

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Acknowledgments

This research was partially supported by a grant from the National Forensic Service (12128139900) and by College of Pharmacy-specialized Research Fund (from institute for new drug development) of Keimyung University in 2012. The authors would like to thank Mr. Hyun-Jin Jung at Agilent Technologies in Korea for technical support.

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Authors and Affiliations

  1. College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu, 704-701, Republic of Korea

    Sooyeun Lee, So-young Kang & Dajeong Ji

  2. National Forensic Service, 331-1 Sinwol-7-dong, Yangcheon-gu, Seoul, 158-707, Republic of Korea

    Seungkyung Baeck & Sangki Lee

  3. Hoseo Toxicology Research Center, Hoseo University, 165 Sechul-ri, Baebang-myun, Asan, Chungcheongnam-do, 336-795, Republic of Korea

    Seung Min Oh

  4. School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, Republic of Korea

    Kyu Hyuck Chung

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  1. Sooyeun Lee
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  2. So-young Kang
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  7. Kyu Hyuck Chung
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Correspondence to Kyu Hyuck Chung.

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Lee, S., Kang, Sy., Ji, D. et al. Quantitative LC–MS/MS method in urine for the detection of drugs used to reverse the effects of chemical castration. Anal Bioanal Chem 405, 3185–3194 (2013). https://doi.org/10.1007/s00216-013-6769-5

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  • DOI: https://doi.org/10.1007/s00216-013-6769-5

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