A Metabolomic Approach Applied to a Liquid Chromatography Coupled to High‐Resolution Tandem Mass Spectrometry Method (HPLC‐ESI‐HRMS/MS): Towards the Comprehensive Evaluation of the Chemical Composition of Cannabis Medicinal Extracts

Abstract

Notwithstanding the use of a standardised starting plant material, great changes are caused by different extraction procedures. The metabolomics approach is a useful tool for the evaluation of the chemical composition of cannabis extracts. Copyright © 2017 John Wiley & Sons, Ltd.

A review on the recent advances in HPLC, UHPLC and UPLC analyses of naturally occurring cannabinoids (2010–2019)

“…Various HPLC and UPLC methods that have been reported for the analysis of cannabinoids in C. sativa L. plant samples and Cannabis consumer products, e.g. hashish, marijuana and cannabis oils, since the year 2010, are summarised in Tables and , and appraised in the following subsections.…”

Developing Robust Standardised Analytical Procedures for Cannabinoid Quantification: Laying the Foundations for an Emerging Cannabis-Based Pharmaceutical Industry

“…In these circumstances, 13 C and 18 O isotopically labelled internal standards would be more appropriate in LC-MS-based cannabinoid quantification, although these standards have limited availability and are typically expensive [75, 76]. Combined with the number of cannabinoids which could be present within heterogeneous CME [27], this presents a challenge for laboratories to source a comprehensive set of isotopically labelled internal standards for the purposes of method validation. Universally labelling biological samples of Cannabis through cultivation under 13 C conditions offers one viable option to generate a sufficient quantity and metabolic range of isotopically labelled reference materials for matrix effect compensation, as well as for the measurement of accuracy and spiked recovery [78].…”

“…However, nominal mass measurements from single mass detectors have limited discriminatory functionality for isomeric compounds [60, 61], such as delta-8- and delta-9-THC. LC-MS/MS with triple quadrupole, quadrupole-time-of flight (Q-TOF) [27, 61, 62] and Orbitrap [63] mass analysers can provide sufficient mass resolution of both parent and fragment ions to allow for discrimination of molecules with identical nominal mass but different elemental arrangements [60, 61]. …”

“…Recent non-targeted profiling of CME using high-resolution LC-MS/MS has revealed a complex chemical fingerprint from ethanolic and plant oil-based extracts, with chemical composition and content dependent not only on the starting material but also on the procedure used for extraction [27]. Other reports that at least five cannabinoid species exhibit a m/z of 315.2294 emphasise the importance of developing analytical procedures with a high level of inherent selectivity [28].…”

“…Whilst a large number of analytical techniques have been employed for the quantification of Cannabis botanical raw material [28], including the monograph Cannabis Flos from the Dutch Office of Medicinal Cannabis, limited attention has been given to the quantification of cannabinoids within Cannabis botanical drug substances or CME [27-29, 52]. This is of significant concern given the effects different extraction protocols could have on sample matrices, the chemical composition of active ingredients [27], storage requirements [45, 53] and subsequent quantitative assessment of cannabinoids. The following sub-sections discuss a validation scheme compliant with the ICH Q2 (R1) guideline and highlight generalised validation parameters for the quantification of cannabinoids within CME, with emphasis on potential challenges for fulfilling these criteria.…”