2537 Bioanalysis (2015) 7(19), 2537–2556 ISSN 1757-6180 Review part of 10.4155/bio.15.172 © 2015 Future Science Ltd Derivatization is one of the most important steps during sample preparation in doping control analysis. Its main purpose is the enhancement of chromatographic separation and mass spectrometric detection of analytes in the full range of laboratory doping control activities. Its application is shown to broaden the detectable range of compounds, even in LC–MS analysis, where derivatization is not a prerequisite. The impact of derivatization initiates from the stage of the metabolic studies of doping agents up to the discovery of doping markers, by inclusion of the screening and confirmation procedures of prohibited substances in athlete’s urine samples. Derivatization renders an unlimited number of opportunities to advanced analyte detection. Since the introduction of chromatographic methods in the determination of xenobiot- ics in biological luids – a ield related to vet- erinary drug analysis, forensic science and doping control analysis – and together with the implementation of chromatographic methods coupled with different types of mass spectrometers for the unquestionable analyte identiication in routine analysis, derivatization procedures have played a central and critical role. The term derivatization is used to describe the procedures in which chemical groups (e.g., protons from protic sites) are replaced by groups that modify physical and chemical properties of analytes, like molecular formula, thermal stability, volatility, polarity, chro- matographic behavior, light absorption, ion- ization ef iciency, mass spectra fragmentation, protection of labile groups, etc, thus resulting in more sensitive and robust detection. For a successful derivatization, a single and stable derivative should be formed for each com- pound and the derivatization reaction should be simply and rapidly performed under mild conditions with a high and reproducible yield. Excellent handbooks and recent reviews are available on the general advantages of derivatization procedures [1–6] . Hundreds of chemically different drugs are included in the List of Prohibited Sub- stances [7] issued by the World Anti-Doping Agency (WADA). The Prohibited List is revised annually and comprises substances grouped according to their pharmacological action. The demanding task of doping con- trol laboratories is to develop analytical methods able to screen a large number of substances, minimizing by the same token, sample preparation and costs. Primarily, doping control analysis requires the use of chromatographic methods [8–10] , particularly GC–MS and LC–MS. Applica- tion of GC–MS and LC–MS for screening purposes is complementary, depending on the properties of the compounds like vola- tility, polarity, molecular weight, ionization properties etc. GC–MS has played major role in the doping control analysis for several decades, despite the increasing use of LC systems in doping control laboratories. The screening beneits from GC–MS (e.g., ionization, cap- illary column chromatographic resolution, etc.) are signiicant, especially for the low ng/ml detection of anabolic androgenic steroids (AAS), since LC–MS ionization for AAS lacking at least a conjugated keto- Current status and recent advantages in derivatization procedures in human doping control Ioanna Athanasiadou 1,2 , Polyxeni Kiousi 3 , Nasia Kioukia-Fougia 3 , Emmanouil Lyris 3 & Yiannis S Angelis* ,3 1 Laboratory of Biopharmaceutics & Pharmacokinetics, Faculty of Pharmacy, National & Kapodistrian University of Athens, Greece 2 Anti-Doping Lab Qatar, Sports City Road, Aspire Zone, P.O. Box 27775, Doha, Qatar 3 Doping Control Laboratory of Athens, Olympic Athletic Center of Athens (OAKA), 15123 Maroussi, Greece *Author for correspondence: Tel.: +30 210 686 8412 Fax: +30 210 683 4021 y_angelis@yahoo.gr For reprint orders, please contact reprints@future-science.com