REVIEW Spectroscopic methods to analyze drug metabolites Jong-Jae Yi 1 • Kyeongsoon Park 2 • Won-Je Kim 3 • Jin-Kyu Rhee 4 • Woo Sung Son 1 Received: 30 June 2017 / Accepted: 16 February 2018 Ó The Pharmaceutical Society of Korea 2018 Abstract Drug metabolites have been monitored with various types of newly developed techniques and/or com- bination of common analytical methods, which could provide a great deal of information on metabolite profiling. Because it is not easy to analyze whole drug metabolites qualitatively and quantitatively, a single solution of ana- lytical techniques is combined in a multilateral manner to cover the widest range of drug metabolites. Mass-based spectroscopic analysis of drug metabolites has been expanded with the help of other parameter-based methods. The current development of metabolism studies through contemporary pharmaceutical research are reviewed with an overview on conventionally used spectroscopic meth- ods. Several technical approaches for conducting drug metabolic profiling through spectroscopic methods are discussed in depth. Keywords Spectroscopy Á Drug metabolites Á Mass spectrometry Á Nuclear magnetic resonance Á Ultraviolet– visible spectroscopy Á Infrared spectroscopy Á Circular dichroism Á Raman spectroscopy Á Surface plasmon resonance Abbreviations ADME/T Absorption, distribution, metabolism, excretion, and toxicity MS Mass spectrometry NMR Nuclear magnetic resonance GC–MS Gas chromatography-mass spectrometry LC–MS Liquid chromatography-mass spectrometry UV–Vis Ultraviolet–visible IR Infrared CD Circular dichroism SEM Scanning electron microscopy ESI Electrospray ionization EI Electron impact ionization MALDI Matrix assisted laser desorption ionization HPLC High-performance liquid chromatography TOF Time of flight DNA Deoxyribonucleic acid MS/MS Tandem mass spectrometry UHPLC Ultra-high performance liquid chromatography FID Free induction decay MHz Megahertz HMBC Heteronuclear multiple-bond correlation HSQC Heteronuclear single quantum coherence HAS Human serum albumin Jong-Jae Yi and Kyeongsoon Park contributed equally. & Jin-Kyu Rhee jkrhee@ewha.ac.kr & Woo Sung Son wson@cha.ac.kr 1 Department of Pharmacy, College of Pharmacy, CHA University, 120 Haeryong-ro, Pocheon-Si, Gyeonggi-do 11160, Republic of Korea 2 Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University, 4726 Seodong-daero, Anseong-Si, Gyeonggi-do 17546, Republic of Korea 3 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea 4 Department of Food Science and Engineering, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea 123 Arch. Pharm. Res. Online ISSN 1976-3786 https://doi.org/10.1007/s12272-018-1010-x Print ISSN 0253-6269