Determination of Scopolamine Distribution in Plasma and Brain by LC-MS/MS in Rats

Abstract

Scopolamine, as a tropane alkaloid found in plants such as belladonna and datura, is used clinically as a transdermal patch and is highly neurotoxic. This study aimed to develop a simple, sensitive, and selective LC-MS/MS method for the determination of the content and distribution of scopolamine in rat plasma and brain after drug administration. In our study, sample pretreatment consisted of protein precipitation with acetonitrile followed by nitrogen blow concentration. Gradient elution of scopolamine and internal standard was performed on a ZORBAX Eclipse Plus C18 (2.1 $\ast$ 100 mm, 3.5 μm) column with water containing 0.1% formic acid (v/v) and acetonitrile as a mobile phase. Those samples were quantified in ESI positive ion mode using an API 4000 triple quadrupole mass spectrometer. The results showed that scopolamine was linear in the calibration range of 2–2500 ng/mL, and the selectivity, accuracy, precision, matrix effect, stability, and recovery of the method were within acceptable limits. The method has been validated and has been successfully used for toxicokinetic studies of scopolamine. After intraperitoneal injection, the time to peak toxic concentrations of scopolamine in rats was 0.5 h. The concentrations of scopolamine in the hippocampus and cortex were much higher than those in the striatum, indicating that the likely targets of its neurotoxic damage were the hippocampus and cortex. Overall, this study provides the basis for the neurotoxicity of scopolamine and provides a reference for its toxicokinetic studies.