LC-MS/MS Quantification of Five Antihistamines in Antemortem Blood: Method Validation and Application

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ID: 324854
2026
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Abstract
Abstract First-generation H1 antihistamines have central nervous system penetration and anticholinergic activity, with potential side effects including sedation, cognitive impairment, anterograde amnesia. First-generation antihistamines pose risks in driving under the influence of drugs (DUID) and drug-facilitated crimes (DFC) forensic casework. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for five first-generation H1 antihistamines: chlorpheniramine, diphenhydramine, doxylamine, hydroxyzine, and promethazine. The calibration range was 1-200 ng/mL with a 1/x linear calibration model for quantitative compounds, and the limit of detection was determined to be 0.5 ng/mL for all compounds. Bias and precision were acceptable, with minor but acceptable suppression observed at low and high concentrations. No exogenous or endogenous interferences were observed. Carryover was not detected after a 400 ng/mL sample. Processed samples were determined to be stable 24 hours after initial injection when stored in the refrigerated multi-sampler. Authentic forensic specimens from DUID and DFC investigations showed a wide range of concentrations for diphenhydramine. Selected case reports are presented to demonstrate the applicability of the method. The high percentage of polysubstance cases, range of concentrations, and delayed sample collection in DFC cases underscore the importance of a sensitive and reproducible method for these first-generation antihistamines, especially in human-performance casework.
Reference Key
openalex_W7202364483 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Kenson Jean, Kristin Kahl, Lisa Reidy
Journal journal of analytical toxicology
Year 2026
DOI
10.1093/jat/bkag074
URL
https://doi.org/10.1093/jat/bkag074
Keywords Keywords not found

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