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Absolute quantitation of propranolol from 200‐μm regions of mouse brain and liver thin tissues using laser ablation‐dropletProbe‐mass spectrometry
Author(s) -
Kertesz Vilmos,
Cahill John F.,
Srijanto Bernadeta R.,
Collier Charles P.,
Vavrek Marissa,
Chen Bingming
Publication year - 2021
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.9010
Subject(s) - chemistry , chromatography , parylene , mass spectrometry , analytical chemistry (journal) , resolution (logic) , laser ablation , propranolol , ablation , biomedical engineering , laser , optics , medicine , physics , organic chemistry , engineering , artificial intelligence , computer science , aerospace engineering , polymer
Rationale The ability to quantify drugs and metabolites in tissue with sub‐mm resolution is a challenging but much needed capability in pharmaceutical research. To fill this void, a novel surface sampling approach combining laser ablation with the commercial dropletProbe automated liquid surface sampling system (LA‐dropletProbe) was developed and is presented here. Methods Parylene C‐coated 200 × 200 μm tissue regions of mouse brain and kidney thin tissue sections were analyzed for propranolol by laser ablation of tissue directly into a preformed liquid junction. Propranolol was detected by high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) in positive electrospray ionization mode. Quantitation was achieved via application of a stable‐isotope‐labeled internal standard and an external calibration curve. Results The absolute concentrations of propranolol determined from 200 × 200 μm tissue regions were compared with the propranolol concentrations obtained from 2.3‐mm‐diameter tissue punches of adjacent, non‐coated sections using standard bulk tissue extraction protocols followed by regular HPLC/MS/MS analysis. The average concentration of propranolol in both organs determined by the two employed methods agreed to within ±12%. Furthermore, the relative abundances of phase II hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous results. Conclusions This work illustrates that depositing a thin layer of parylene C onto thin tissue prior to analysis, which seals the surface and prevents direct liquid extraction of the drug from the tissue, coupled to the novel LA‐dropletProbe surface sampling system is a viable approach for sub‐mm resolution quantitative drug distribution analysis.