Direct Analysis of Glucuronides with Liquid Chromatography-Mass Spectrometric Techniques and Methods

Raimo      A. Ketola; Kati      S. Hakala

Abstract

Glucuronidation is one of the main phase II metabolic reactions in humans and animals. A variety of analytical techniques and methods have been used for the detection and quantification of glucuronides of both endogenous and xenobiotic compounds from different biological samples of humans and animals. Drug metabolism has been extensively studied with both in vitro and in vivo experiments under various conditions. The purpose of this review is to explore in detail the benefits and drawbacks of different liquid chromatography- mass spectrometric (LC/MS) methods and techniques in detection and identification of all forms of glucuronide conjugates from in vitro, biological, and environmental samples. The entire analytical procedure is covered, from sample treatment, separation, and ionization to qualitative and quantitative analyses. The aim of this review is not to cover every published paper where glucuronides are identified and/or quantified, but rather to focus on special cases where a new analytical approach or technical development has led to a better, more specific, or more comprehensive detection, identification, or quantitation of glucuronide conjugates.

Keywords: Glucuronidation, glucuronide, metabolism, drug, LC/MS, tandem mass spectrometry, determination, analysis, uridine diphosphate, UDP, glucuronosyltransferases (UGTs), uridine 5'-diphosphoglucuronic acid (UDPGA), b-D-glucopyranosiduronic acid, high-performance liquid chromatography, liquid chromatography-mass spectrometry, proton nuclear magnetic resonance spectroscopy, buprenorphine, norbuprenorphine glucuronides, liquid-liquid extraction, Morphine-3-glucuronide, morphine-6-glucuronide, Meconium, Acylglucuronides, Steroid glucuronides, liquid-phase microextraction, anabolic androgenic steroid, mycophenolic acid, 9-tetrahydrocannabinol-9-carboxylic acid, Hydrophilic interaction liquid chromatography, aglycone, Develosil ODS-HG-5 column, amammonium acetate, acetonitrile, flurbiprofen glucuronides, S-flurbiprofen b-alanine conjugate, trans-7S,8S-dihydrodiol, benzo(a)pyrene dihydrodiols, electrospray ionization, atmospheric pressure chemical ionization, atmospheric pressure photoionization, 4-hydroxy-3-methoxymethamphetamine- glucuronide, carvedilol, estriol glucuronide, chloro-1-methylpyridinium iodide, ethyl-3-(3-dimethylaminopropyl) carbodiimide, 2-picolylamine, Carbamoylglucuronides, apigenin-7-O-diglucuronide, luteolin-7-O-diglucuronide, 4-hydroxy-3-methoxymethamphetamine, 5-hydroxytryptophol glucuronide