Key result
Optimized LC-MS/MS protocol detects activated doxorubicin at 7.8 pg in mouse tumor models.
Why the study?
The localized conversion of inactive doxorubicin prodrug chemotherapeutics to active forms is difficult to quantify in mouse tumor models due to small tissue regions involved.
The described LC-MS/MS method enables highly sensitive quantification of doxorubicin and its prodrugs in mouse tumor models, which is useful for determining biodistribution and activation efficiency.
May enhance preclinical doxorubicin prodrug studies in mice; leaves open human translation and validation.
The localized conversion of inactive doxorubicin prodrug chemotherapeutics to pharmacalogically active forms is difficult to quantify in mouse tumor models because it occurs only in small regions of tissue. The tumor tissue extraction protocol and LC-MS/MS analysis method described here were optimized to obtain a detection limit of 7.8 pg for the activated doxorubicin and 0.36 ng for the doxorubicin prodrug. This method can be useful for determining the biodistribution and activation efficiency for many different doxorubicin prodrugs. It can also be used for quantification of doxorubicin from tumor models that have poor vascularization resulting in low tissue accumulation.
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Ibsen et al. (2013) studied mouse tumor models. Tumor tissue extraction protocol and LC-MS/MS analysis method was evaluated on Detection limit for activated doxorubicin and doxorubicin prodrug. An optimized tumor tissue extraction protocol and LC-MS/MS method achieved a detection limit of 7.8 pg for activated doxorubicin and 0.36 ng for doxorubicin prodrug in mouse tumor models.
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