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.

 

Antibody-Drug Conjugates (ADCs) are antibodies engineered to deliver a cytotoxic agent specifically to tumor cells expressing a defined antigen. Compared to the bioanalysis of small molecules or recombinant proteins, the bioanalysis of ADCs is much more challenging due to the complexity of the drug. Multiple species are present in the circulation that can provide additional information on clinial safety and efficacy.

We present in this poster the strategy used for the bioanalysis of antibody-drug conjugates, combining immunoassays and LC/MS. A focus is put on mass spectrometry techniques and their use for the quantification of the antibody, the determination of the drug-to-antibody ratio and the quantification of the small molecule species.