Tetrahydropalmatine Poisoning: Diagnoses of Nine Adult Overdoses Based on Toxicology Screens by HPLC with Diode-Array Detection and Gas Chromatography–Mass Spectrometry

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Abstract
Background: Tetrahydropalmatine (THP) is a neuroactive alkaloid with analgesic and hypnotic action. Its analysis is important because cases of human poisonings have emerged as a result of unregulated use of some proprietary biopharmaceuticals containing purified THP. Methods: We established analytical parameters for HPLC with diode-array detection (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 μmol/L). Paired analyses of urine with and without glucuronidase treatment clarified the disposition of THP. Our GC–MS method with trimethylsilane derivatization identified O-desmethyl metabolites. With a uniform solid-phase extraction, the HPLC-DAD procedure detected intact glucuronide metabolites. Conclusion: Intact glucuronide metabolites of THP are sensitive markers for THP exposures. Our methods and findings provide practical tools and information for surveillance of intoxication caused by excessive THP intake.