title: Determination of norcantharidin in mouse tissues by liquid chromatography coupled to tandem mass spectrometry and its tissue distribution study.
abstract: The purpose of this study is to determine the concentrations of norcantharidin (CAS NO: 5442-12-6) in mouse tissues and investigate its tissue distribution after intragastric administration of disodium norcantharidate solution. A highly sensitive and specific liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated, using ribavirin (CAS NO: 36791-04-5) as the internal standard (IS). Norcantharidin and IS were extracted from 0.3 mL tissue homogenates using protein precipitation with acetone under acid condition. The analyte was separated on a C18 reverse phase column and analyzed by MS/MS in the multiple reaction monitoring (MRM) mode using ESI with positive ionization, m/z 169→123 for norcantharidin and m/z 267→135 for IS. The developed method was validated over a linear range of concentrations 0.01~5 μg·mL - 1 in liver, lung, kidney, stomach, small intestine, uterus and testis, 0.005~0.5 μg·mL - 1 in heart, spleen and brain, the correlation coefficients (r2) were between 0.9918 and 0.9976. The tissue distribution study result was as follows: The AUC0-t of norcantharidin in tissues was in the order as follows: small intestine, stomach, uterus, kidney, testis, liver, lung, spleen, heart, brain.
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Yuan
authors.forename: C
authors.initials: C
authors.lastname: Wei
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Gao
authors.forename: R
authors.initials: R
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis* / Q000493:pharmacokinetics*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000032:analysis* / Q000493:pharmacokinetics*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007441:Intubation, Gastrointestinal; D057230:Limit of Detection; D008297:Male; D051379:Mice; D019999:Pharmaceutical Solutions; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D019999:Pharmaceutical Solutions; D012996:Solutions; C069741:norcantharidin