Multi-drug chemotherapy dose optimisation in preclinical leukaemia models using HPLC-MS/MS

Translation of novel drug combinations to clinical trials requires testing of drugs in carefully designed in vivo experiments. In the literature, the doses of chemotherapeutic drugs vary drastically across preclinical studies and selection of the clinically relevant and non-toxic doses is challenging. Moreover, in childhood leukaemia where repurposing of existing drug therapies and novel drug combinations are generating interests, it has become difficult to identify the appropriate dosages to undertake preclinical studies. To address this, we have developed analytical methods to quantify plasma drug levels in mice of multiple-drugs for a novel quadruple drug combination developed for the treatment of ALL. After drug administration to mice, small volumes of plasma were collected at appropriate time points and drug concentrations in plasma were calculated using an HPLC-MS/MS system. This strategy allowed us to identify and adjust the dosages of drugs whilst assessing toxicity without excessive use of animals. Quantification of drug plasma levels in mice guided the selection of clinically applicable doses.

 

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Artikel online veröffentlicht:
13. Mai 2020