Detection and Mapping of Cannabinoids in Single Hair Samples through Rapid Derivatization and Matrix-Assisted Laser Desorption Ionization Mass Spectrometry

Abstract

The sample preparation method reported in this work has permitted for the first time the application of matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) profiling and imaging for the detection and mapping of cannabinoids in a single hair sample. MALDI-MS imaging analysis of hair samples has recently been suggested as an alternative technique to traditional methods of GC/MS and LC/MS due to simpler sample preparation, the ability to detect a narrower time frame of drug use, and a reduction in sample amount required. However, despite cannabis being the most commonly used illicit drug worldwide, a MALDI-MS method for the detection and mapping of cannabinoids in a single hair has not been reported. This is probably due to the poor ionization efficiency of the drug and its metabolites and low concentration incorporated into hair. This research showed that in situ derivatization of cannabinoids through addition of an N-methylpyridium group resulted in improved ionization efficiency, permitting both detection and mapping of Δ-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), and the metabolites 11-nor-9-carboxy-Δ-tetrahydrocannabinol (THC-COOH), 11-hydroxy-Δ-tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-Δ-tetrahydrocannabinol glucuronide (THC-COO-glu). Additionally, for the first time an in-source rearrangement of THC was observed and characterized in this paper, thus contributing to new and accurate knowledge in the analysis of this drug by MALDI-MS.

Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights

“…These standards could be included as early in the workflow as dosing the animals/cells up to right before the ions enter the instrument. 2,28,29 For MALDI, the standards are typically applied prior to matrix application using the same automatic sprayer systems described below. 30–32 Chumbley et al has done a comprehensive study to determine the proper inclusion of the standard (e.g., with matrix, under the tissue section, or sandwiching the section with matrix), and it was found that depositing the standards followed by matrix to be optimal for MSI mapping of spatial distribution of the drug rifampicin.…”

“…31,53 Other steroids (e.g., tetrahydrocannabinal) have also been targeted using 2-fluoro-1-methylpyridinium p -tolunesolfonate as a derivatization agent. 29 N-glycans (Figure 2), fatty acids, and neurotransmitters have all been targets through other, unique on-tissue assays. 28,42,52 Compared to the traditional spraying of reagent, which usually produces poor spatial resolutions (>100 µ m), electrospray deposition has been successfully utilized to derivatize fatty acids while achieving a high spatial resolution (20 µ m).…”

“…This may come with their broad diversity, as they include TCA cycle components, 1,218,233 neurotransmitters, 2,28 drugs, 29 and even fungicides. 234 Importantly, these diverse small molecule metabolites could be indicative of disease state.…”

“…234 Importantly, these diverse small molecule metabolites could be indicative of disease state. 152,218 Some of the more notable applications include imaging tetrahydrocannabinol (THC) in hair strands (Figure 7), 29 determination of antimicrobial metabolites for biocontrol against F. oxysporum , 235 and metabolomic distribution analysis of kidney metabolites after rats being treated with furosemide. 36 Because of their structure, metabolites can have poor ionization efficiency, which has prompted the development of many derivatization schemes to increase access to metabolites in samples.…”

Microsegmental Analysis of a Single Hair Strand: Pushing the Envelope on Hair Drug Testing

“…The analysis of a very short segment, in the submillimeter range, from a single hair strand is now possible with modern analyzers. Sensitive methods involving gas chromatography/tandem mass spectrometry, LC/MS/MS, and MALDI mass spectrometric imaging have been described for single-strand hair drug analysis (10)(11)(12). MALDI mass spectrometric imaging requires less sample preparation but is less sensitive than LC/MS/MS.…”