The present study aimed to (i) develop a sensitive LC-MS/MS-based technique for simultaneous detection and quantification of Imidacloprid (IMI) and its metabolites in tissue specimens, and to (ii) determine the specific bioaccumulation trends of the IMI compounds in organs of C57BL/6J male mice; after exposure to 0.6 mg/kg bw/day of IMI (10% of NOAEL) through a powdered diet for 24 weeks. We successfully developed a method which was accurate (recoveries were ≥ 70% for most compounds), sensitive (LODs ≤ 0.47 ng/mL, LOQs ≤ 1.43 ng/mL and R2 ≥ 0.99) and precise (RSDs ≤ 20%) for routine analysis of IMI and seven of its metabolites in in blood and various tissues of mice. Upon biodistribution analysis, IMI and five of its metabolites were detected in various organs within mice. Blood, liver, mesenteric white adipose tissue and pancreas mainly accumulated IMI-olefin; brain, testis, inguinal white adipose tissue and gonadal white adipose tissue mainly accumulated IMI, whereas the kidney mainly accumulated 4-hydroxy-IMI. The N-desnitro-IMI metabolite showed unique accumulation in brain and testis by recording brain-blood and testis-blood detection ratios of 8.4 and 7.6, respectively. Cumulative levels of the six detected IMI compounds (Σ6 IMI compounds) were found in the decreasing order; blood > testis > iWAT > kidney > brain > gWAT > mWAT > pancreas > liver. The current study provides essential data needed for effective mechanistic elucidation of compound-specific adverse outcomes associated with chronic exposures to IMI in mammalian species.
