Determination of sibutramine and metabolites M1 and M2 in human blood and tissue samples by LC-MS/MS and its forensic application

This study aimed to establish a new method for quantitating sibutramine and its Phase I metabolites M1 and M2 in human blood and tissues using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technology to evaluate the safety in poisoning cases. The method was fully validated for human blood and six tissue samples. The detection was linear from 1 to 100 ng/mL (r² >0.99). These threshold values were sufficiently sensitive to detect sibutramine and its metabolites in various biological samples. The stabilities, biases/accuracies, and overall precision were verified. Over 80% of the samples in seven complex biological matrices exhibited acceptable soft matrix effects (≤ ± 25%) and good recoveries (>60%). The method was then applied to analyse samples from a suspected case of sibutramine poisoning in which the accumulated drug concentration was higher in the liver and heart. The results validated the method’s suitability for analysing blood and tissue samples with high sensitivity and good reproducibility, and they provide significant information for selecting materials for subsequent similar cases. These results further confirm that because sibutramine is a weight-loss drug with health risks, its social and market control should be strengthened.