Pharmacokinetic study based on a matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight imaging mass microscope combined with a novel relative exposure approach: A case of octreotide in mouse target tissues

Abstract

Application of imaging mass spectrometry in drug pharmacokinetics remains challenging due to its weak quantitative capability. Herein, an imaging mass microscope (iMScope), equipped with an optical microscope, an atmospheric pressure ion-source chamber for matrix-assisted laser desorption/ionization (AP-MALDI) and a hybrid quadrupole ion trap time-of-flight (QIT-TOF) analyzer, was first validated and applied to visualize drug disposition in vivo. The distribution and elimination rate of the therapeutic peptide octreotide, a long-acting analogue of the natural hormone somatostatin, was first calculated based on the data determined by iMScope system combining a novel relative exposure strategy. Microspotted pixel-to-pixel quantitative iMScope provided a relative amount of octreotide presented in a thin stomach/intestinal section while preserving its original spatial distribution. The images of dosed mouse stomach clearly demonstrated the transport process of octreotide from the mucosal layer to the muscle side. More importantly, octreotide was found to eliminate from the intestines rapidly, the absorption peak time (Tmax) appeared at 40 min and the half-life time (t1/2) was calculated as 37.7 min according to the elimination curves. Comparisons to the LC-MS/MS data adequately indicated that the quantification approach and methodology based on the iMScope was reliable and practicable for drug pharmacokinetic study.