ArticleAnalytical and bioanalytical chemistry2026
Comprehensive metabolic profiling of the new designer stimulant MDPiHP-in vitro and in vivo identification of potential biomarkers for detection in human samples.
Article in Analytical and bioanalytical chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Phase I metabolism of the methadone analog methiodone (IC-26) in pooled human liver microsomes and its detection in seven authentic human cases.Archives of toxicology · 2026Article
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6 authors.
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Abstract
New psychoactive substances (NPS) pose an increasing threat to public health. Synthetic cathinones are among the most prevalent subclasses of NPS in Europe. Recently, MDPiHP (3,4-methylenedioxy-α-pyrrolidinoisohexanophenone), a positional isomer of MDPHP (3,4-methylenedioxy-α-pyrrolidinohexanophenone), has been detected in several seizures across Europe. However, its pharmacological and toxicological profiles remain unknown. In this study, we report the first investigation of MDPiHP metabolism, combining in vitro pooled human liver microsome (pHLM) experiments and the analysis of authentic human biological samples, including urine, blood, serum, and plasma. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QToF-MS) enabled the tentative identification of eleven metabolites in the in vitro assay. The most abundant metabolite was dimethyl-MDPiHP (M8), followed by dihydro-MDPiHP (M1.2) and hydroxy-MDPiHP (M2.3). In human biological samples, 22 metabolites were detected. The most abundant were dihydro-MDPiHP (M1.2) and M3, generated through pyrrolidine ring hydroxylation followed by ring opening and terminal carboxylation. Together with the parent compound, these metabolites are proposed as biomarkers of intake. A limitation of this study is the known instability of synthetic cathinones in biological matrices. This may alter metabolite ratios, and consequently, parent compound levels may be underestimated. A comparison between in vitro and in vivo findings revealed differences in the formation of metabolites, underscoring the limitations of the pHLM model in fully reproducing human metabolic complexity. The comprehensive metabolic profile described provides essential information for clinical and forensic toxicology, enabling the reliable detection of MDPiHP use and laying the groundwork for further studies on its toxicity and pharmacokinetics.
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