Liquid chromatography–electrospray mass spectrometry determination of ibogaine and noribogaine in human plasma and whole blood: Application to a poisoning involving Tabernanthe iboga root

A liquid chromatography/electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the first time for the determination of ibogaine and noribogaine in human plasma and whole blood. The method involved solid phase extraction of the compounds and the internal standard (fluorescein) from the two matrices using Oasis®HLB columns. LC separation was performed on a Zorbax eclipse XD8 C8 column (5 μm) with a mobile phase of acetonitrile containing 0.02% (v/v) trimethylamine and 2 mM ammonium formate buffer. MS data were acquired in single ion monitoring mode at m/z 311.2, 297.2 and 332.5 for ibogaine, noribogaine and fluorescein, respectively. The drug/internal standard peak area ratios were linked via a quadratic relationship to plasma (0.89–179 μg/l for ibogaine; 1–200 μg/l for noribogaine) and to whole blood concentrations (1.78–358 μg/kg for ibogaine; 2–400 μg/kg for noribogaine). Precision ranged from 4.5 to 13% and accuracy was 89–102%. Dilution of the samples had no influence on the performance of the method. Extraction recoveries were ≥94% in plasma and ≥57% in whole blood. The lower limits of quantitation were 0.89 μg/l for ibogaine and 1 μg/l for noribogaine in plasma, and 1.78 μg/kg for ibogaine and 2 μg/kg for noribogaine in whole blood. In frozen plasma samples, the two drugs were stable for at least 1 year. In blood, ibogaine and noribogaine were stable for 4 h at 4 °C and 20 °C and 2 months at −20 °C. The method was successfully used for the analysis of a poisoning involving Tabernanthe iboga root.