Tetrahydropalmatine poisoning: Diagnoses of nine adult overdoses based on toxicology screens by HPLC with diode-array detection and gas chromatography mass spectrometry

Background: Tetrahydropalmatine (THP) is a neuroactive alkaloid with analge sic and hypnotic action. Its analysis is important because cases of human p oisonings have emerged as a result of unregulated use of some proprietary b iopharmaceuticals containing purified THP. Methods: We established analytical parameters for HPLC with diode-array det ection (HPLC-DAD) and gas chromatography-mass spectrometry (GC-MS) for the detection of THP in serum and urine. Nine acutely THP-poisoned adults were thus screened over 16 months. Results: All patients recovered quickly after mild neurological disturbance . In general, THP was metabolized rapidly and excreted as polar metabolites in urine. Serum THP was measured in five cases and found to be <0.1-1.2 mg /L (<0.3-3.4 mu mol/L). Paired analyses of urine with and without glucuroni dase treatment clarified the disposition of THP. Our GC-MS method with trim ethylsilane derivatization identified O-desmethyl metabolites. With a unifo rm solid-phase extraction, the HPLC-DAD procedure detected intact glucuroni de metabolites. Conclusion: Intact glucuronide metabolites of THP are sensitive markers for THP exposures. Our methods and findings provide practical tools and inform ation for surveillance of intoxication caused by excessive THP intake.