Technologies and strategies to characterize and quantitate metabolites in drug discovery and development

Abstract

Pharmacokinetics and toxicokinetics studies rely on the quantitation of drugs and its metabolites. Drug metabolism studies are based on the characterization of the structure of drugs and their metabolites. Liquid chromatography coupled with mass spectrometry is an undisputed technology for the routine analysis of drugs and metabolites in the drug discovery set-up. Advancements in liquid chromatography and mass spectrometry have accelerated and improved drug discovery and development. Identification and quantitation of drugs and metabolites have gained importance because of their relevance to clinical research. In the present review, we present a bird's eye view of qualitative and quantitative analysis of drugs and their metabolites. Various technologies available to characterize and quantitate metabolites are analyzed. Characterization of metabolites of the sulfonyl urea drug glyburide and the kinetics of glyburide metabolism are discussed in detail.

Investigation of diltiazem metabolism in fish using a hybrid quadrupole/orbital trap mass spectrometer

“…Most studies have focused on mammalian tissue to investigate therapeutic effects and the pharmacokinetics of drugs. One study on techniques for drug and drug metabolite discovery described a semi‐quantitative approach that could be used to perform quantification . There have been a couple of subsequent studies where this technique was applied for the quantification of metabolites formed in vitro in rat blood plasma and in a liver homogenate containing all the metabolizing enzymes present in the human liver (instead of human liver microsomes) …”

Microbioreactors and Perfusion Bioreactors for Microbial and Mammalian Cell Culture

“…Organ-on-a-chip [17] is an ongoing research to hasten the process of drug discovery and development. In vitro drug screening and safety testing [18][19][20] are essential to minimize extensive studies on laboratory animals. Microbioreactors designed as per the need of the study will be highly beneficial to understand the potency and toxicity of the developed drug molecules.…”

In Vitro Biotransformation in Drug Discovery

“…Metabolites are identified and characterized using liquid chromatography and mass spectrometry (LC-MS/MS) [10]. In vitro biotransformation studies performed on various species guides the researchers to choose the right animal model to validate the developed molecule [11,12].…”

“…Liquid chromatography also provides a vital information to purify the drugs, metabolites and nano materials that serves as delivery systems for various biomedical applications [13,14]. Mass Spectrometry resort to identify the mass of the drugs, metabolites and thus helpful to assign the biotransformation sites in the metabolites [10,12].…”