Chromatographic bioanalytical assays for targeted covalent kinase inhibitors and their metabolites

• Targeted covalent kinase inhibitors (TCKIs) are an emerging new class of TKIs. Over 50% methods use protein precipitation for treating TCKI samples. Reversed-phase LC is the separation technique used in almost all bioaakttical assays. 85% a triple quadrupole MS as detector TCKIs bioanalysis. High-resolution more qualitative investigations TCKIs. Deriving from targeted (TKIs), TKIs that covalently bound to their target residue receptors. Currently, there many under clinical development besides afatinib, ibrutinib, osimertinib, neratinib, acalabrutinib, dacomitinib, and zanubrutinib already approved by FDA. Subsequently, increasing demand bioanalytical qualitatively quantitively investigate those compounds, leading number papers reporting development, validation, Most publications describe technological set up analytical allow quantification various biomatrices such plasma, cerebrospinal fluid, urine, tissue, liver microsomes. In addition, identification metabolites biotransformation pathways has gained interest recent years. We provide overview this The included issues sample pretreatment, chromatographic separation, detection, method validation. scope bioanalysis TCKIs, mostly applied treat biological matrices sample. Liquid reversed-phase mode (RPLC) mass detection with (QqQ) most often utilized quantitative modes, respectively. There may be possibility increased high-resolution spectrometry (HRMS) investigation purposes future. also found US FDA EMA guidelines common employed validation framework