Bente Gammelgaard1, Helle Rüsz Hansen, Stefan Stürup, Charlotte Møller. 1. Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. bg@farma.ku.dk
Abstract
BACKGROUND: The inherent properties of element selectivity combined with high sensitivity and structure independent response, make inductively coupled plasma mass spectrometry (ICP-MS) an interesting alternative detection technique in drug metabolism studies. OBJECTIVE: The application of online separation with ICP-MS detection in drug metabolism studies is reviewed with focus on the merits and demerits of this detection technique. The prerequisite for inclusion in this review is that the study involves a separation technique hyphenated online to the ICP-MS detection. RESULT/ CONCLUSION: ICP-MS detection is found to be advantageous for analysis of all drug substances detectable by ICP-MS compared to radiochemical detection. Detectable drugs are limited to halogen-, sulfur-, metal- and metalloid-containing compounds. The drawback of interference from endogenous compounds on quantitative mass balance estimations of non-metal drugs is addressed. The potential of determining the stoichiometry in metallo-drug biomolecule interactions is pointed out by presenting examples of simultaneous monitoring of metals in metallo-drugs and intrinsic ICP-MS detectable elements in biomolecules. It is concluded that ICP-MS detection is an indispensable technique in drug metabolism studies of metallo-drugs, although the applicability for traditional drugs is limited.
BACKGROUND: The inherent properties of element selectivity combined with high sensitivity and structure independent response, make inductively coupled plasma mass spectrometry (ICP-MS) an interesting alternative detection technique in drug metabolism studies. OBJECTIVE: The application of online separation with ICP-MS detection in drug metabolism studies is reviewed with focus on the merits and demerits of this detection technique. The prerequisite for inclusion in this review is that the study involves a separation technique hyphenated online to the ICP-MS detection. RESULT/ CONCLUSION: ICP-MS detection is found to be advantageous for analysis of all drug substances detectable by ICP-MS compared to radiochemical detection. Detectable drugs are limited to halogen-, sulfur-, metal- and metalloid-containing compounds. The drawback of interference from endogenous compounds on quantitative mass balance estimations of non-metal drugs is addressed. The potential of determining the stoichiometry in metallo-drug biomolecule interactions is pointed out by presenting examples of simultaneous monitoring of metals in metallo-drugs and intrinsic ICP-MS detectable elements in biomolecules. It is concluded that ICP-MS detection is an indispensable technique in drug metabolism studies of metallo-drugs, although the applicability for traditional drugs is limited.
Authors: Sarah Theiner; Márkó Grabarics; Luis Galvez; Hristo P Varbanov; Nadine S Sommerfeld; Mathea S Galanski; Bernhard K Keppler; Gunda Koellensperger Journal: Dalton Trans Date: 2018-04-17 Impact factor: 4.569