Quantification of deuterated levodopa and metabolites in plasma and urine
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.
Presented by
Nico van de Merbel,
Senior Director of Bioanalytical Science
Nico van de Merbel is Senior Director of Bioanalytical Science at the Bioanalytical Laboratory of PRA Health Sciences in The Netherlands.
His field of expertise is the bioanalytical application of chromatographic methods for small and large molecules. He is responsible for research, method development and validation of LC-MS methods for biological samples.
Nico obtained his M.Sc. in toxicology and his Ph.D. in analytical chemistry at the Free University in Amsterdam. He holds an honorary professorship in Industrial Bioanalysis at the University of Groningen.
He has over 30 years of experience in quantitative bioanalysis in academia and industry and has been employed with Pharma Bio-Research/PRA since 1995.
