抄録
MSI, known to bring molecular distribution information, allows quantification. This has been established with QWBA but it lacks the ability to differentiate between drug components&establish separate quantitative results for each target.This demonstrates our capabilities as complementary to QWBA to follow chloroquine&its metabolites at different time-points after an administration of a radiolabeled dose to rats; euthanized at 4,24,72,168&336h post-dose.Carcasses were frozen in a hexane/dry ice bath,embedded in chilled carboxymethylcellulose&frozen into blocks. QWBA images were obtained following exposure to phosphorimaging screens&scanned using a GE Typhoon scanner. QWBA images were quantified against 14Cfortified standards using MCIDTM. For QMSI, MALDI matrix spiked with labeled chloroquine-d4&its metabolite desethyl chloroquine-d4 were sprayed onto the slide. Analyses were performed by a MALDI-FTICR in the head:the eye& in the mid whole-body region. 1H-Chloroquine&1H-desethyl chloroquine were detected by MALDI-FTICR in the eye: uveal tract, vitreous humor...In the mid whole-body region, 2compounds were detected in organs from T4h sections.2compounds were co-localized into the tissue sections&distributions matched the zones obtained by QWBA.The advantage’s the ability to discriminate between parent drug 1H-choloroquine&its metabolite 1H-desethyl chloroquine so that each compound had its own distribution image&its quantification data.The used labeled forms of both compounds during the matrix deposit allowed normalizing the data for each position with the MALDI onto the section of interest&calibration range of both 1H-choloroquine&1H-desethyl chloroquine and quantifying each compound into the organs of interest with the ILC.QMSI demonstrate the disappearance of the drug &its metabolite with time to understand differential pharmacokinetic demonstrating the additional input of the technology compared to QWBA.
