Laura Friederich’s scientific contributions

PurposeKratom is a botanical drug with psychoactive properties that is increasingly being used recreationally and “therapeutically” in a non-medically supervised setting. Analytical methods for the detection of kratom use in biological matrices are limited in scope. Prevalence of these alkaloids and their metabolites in forensic specimens is not well understood. The purpose of this study was to develop and validate a procedure to identify five Mitragyna alkaloids in blood and tissues using liquid chromatography quadrupole time–of–flight mass spectrometry (LC–Q/TOF–MS).Methods Mitragynine (MG), speciociliatine (SC), paynantheine (PY), speciogynine (SG) and 7-hydroxymitragynine (7-MG-OH) were identified in postmortem blood (n = 40) and liver specimens (n = 20). Mitragyna alkaloids were determined quantitatively using targeted acquisition and metabolites were identified qualitatively using full scan (untargeted) acquisition.ResultsThe analytical procedure was validated in accordance with published recommendations. Limits of quantitation were 0.5–2 ng/mL for the five targeted alkaloids. Precision, bias, and matrix effects were all within acceptable thresholds. Concentrations of MG in central and peripheral blood were 1–422 ng/mL and 1–412 ng/mL. Liver concentrations of MG ranged from < 4 to > 1450 ng/g. Metabolites of MG (7-MG-OH, 9-O-demethylmitragynine and 16-carboxymitragynine) were also identified in postmortem blood with 7-MG-OH being identified in at least 95% of cases. Interestingly, SC concentrations were frequently identified in excess of MG concentrations.ConclusionsA validated LC–Q/TOF–MS method for the analysis of five Mitragyna alkaloids is described. In addition, minor Mitragyna alkaloids and metabolites can serve as biomarkers of kratom use in blood and tissues.

Mitragynine is the primary active alkaloid in the leaves of the tropical tree Mitragyna speciosa, and goes by the popular names "Kratom", biak-biak and maeng da. Mitragynine is increasingly seen in forensic toxicology casework including driving under the influence of drugs and medicolegal death investigation cases. The toxicity of mitragynine continues to be debated in the scientific community as advocates highlight its long history of use in Southeast Asia and testimonials to its benefits by present-day users, while opponents point to an increasing number of adverse events tied to mitragynine use in Western societies. Quantitative reports of mitragynine in biological specimens from forensic investigations in the literature are sparse and may be influenced by poor analyte stability and inadequate resolution of mitragynine from its diastereomers, which could lead to falsely elevated concentrations and subsequently render those reported concentrations inappropriate for comparison to a reference range. Over the course of 27 months, 1,001 blood specimens submitted to our laboratory tested positive for mitragynine using a sensitive and specific quantitative LC-MS/MS method; concentrations ranged from 5.6-29,000 ng/mL, with mean and median concentrations of 410 ± 1,124 and 130 ng/mL, respectively. Mitragynine presents an analytical challenge that requires a method that appropriately separates and identifies mitragynine itself from its isomers and other related natural products. We describe a validated analytical method and present a short series of case reports that provide examples of apparent adverse events, and the associated range of mitragynine concentrations. This type of analytical specificity is required to appropriately interpret mitragynine concentrations detected in biological specimens from forensic casework and assess its potential toxicity.