Although most bioanalytical methods for pharmacokinetic and pharamcodynamic purposes are based on LC-MS/MS, this technique does not accomodate the analysis of certain groups of analytes among which elemental impurities. The most appropriate technique for multi-elemental bioanalysis is ICP-MS. It is highly sensitive (LODs in the pg-ng/mL range), relatively free from interferences, the linearity of the response is wide (up to 5 orders of magnitude for biological samples) and it allows high throughput analysis.
Methods for the simultaneous determination of 9 elements (Al, As, Ba, Cd, Co, Hg, Ni, Pb and V) in human whole blood and urine were developed and validated in compliance with the international regulations presented in « Guideline on bioanalytical validation, EMA, July 2011 » and « FDA Guidance for Industry: Bioanalytical method Validation ». Those methods were subsequently used for analysing samples from a clinical study with the objective of assessing the concentration of these Class I and IIa elemental impurities in blood and urine.