In recent years, there has been a growing interest in exploring the potential of deuterated drugs. Selective replacement of 1 or more hydrogen atoms in a drug molecule by deuterium can slow down the metabolism of the drug, leading to improved properties.
To assess the in vivo fate of deuterated drugs and to compare their pharmacokinetics, metabolism and excretion with those of corresponding non-deuterated molecules, it is important to quantify the deuterated drug, its relevant metabolites and all non-deuterated counterparts in various bioanalytical fluids using mass spectrometry.
In this webinar, we will describe a bioanalytical approach to monitoring the triply deuterated drug candidate levodopa and 5 of its metabolites plus its endogenously occurring non-deuterated forms in human plasma and urine. Because of the relatively low relevant analyte concentrations, 2 derivatization reactions were employed, followed by LC-MS/MS quantification of the derivatized deuterated and non-deuterated compounds plus a set of internal standards. Special attention will be paid to the mass spectrometric interference of the naturally occurring heavy stable isotopes (¹³C, ³³S and ³⁴S) of the non-deuterated analyte derivatives in the MS/MS transition of the deuterated molecules.
In conclusion, we will demonstrate that deuterated and non-deuterated analytes can be quantified together using LC-MS/MS, but overestimation of the concentrations of the deuterated molecules may be unavoidable, and a careful interpretation of the concentration data is essential.
Key Learning Objectives
- How to apply LC-MS/MS to support the development of deuterated rugs
- How to approach the simultaneous quantification of deuterated and non-deuterated compounds
- How to select proper internal standards for deuterated drug assays
- How to evaluate the possible interference of natural heavy isotope forms of the non-deuterated compounds
