Fast and sensitive UHPLC-MS/MS analysis of cannabinoids and their acid precursors in pharmaceutical preparations of medical cannabis and their metabolites in conventional and non-conventional biological matrices of treated individual

Pichini, Simona; Mannocchi, Giulio; Gottardi, Massimo; Pérez-Acevedo, Ana Pilar; Poyatos, Lourdes; Papaseit, Esther; Pérez‐Mañá, Clara; Farré, Magı́; Pacifici, Roberta; Busardò, Francesco Paolo

doi:10.1016/j.talanta.2019.120537

Cited by 42 publications

(57 citation statements)

References 18 publications

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“…The literature search yielded a total of 363 results, 26 of which met our inclusion criteria ( Figure 1 ) [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. These studies are summarized in Table 1 , Table 2 , Table 3 and Table 4 .…”

Section: Resultsmentioning

confidence: 99%

“…In this section, we only considered the administration of oil-based cannabis (see above for capsules containing oil). Only three studies were found in which oil was directly ingested [ 43 , 52 , 53 ]. Among these three studies, only two reported single-dose administrations.…”

Section: Resultsmentioning

confidence: 99%

“…The subject received 0.45 mL of oil containing 0.95 mg of THC, 1.5 mg of THCA-A, 0.86 mg of CBD, and 2.8 mg of cannabidiolic acid (CBDA). The THC and THCA-A Cmax in serum following oil administration were 0.5 and 40.3 ng/mL, respectively, with a Tmax of 2.0 h for both cannabinoids [ 53 ]. See Table 2 for the specific results.…”

Section: Resultsmentioning

confidence: 99%

“…Decoctions are also called “tea” in several articles. Only three studies examining cannabinoid PK after cannabis decoction administration were retrieved, including one study with a milk decoction [ 41 , 52 , 53 ]. For the milk decoction, two doses were selected—a low THC dose of 16.5 mg and a high dose of 45.7 mg, achieving a Cmax of 3.8 and 8.4 ng/mL, respectively, and a Tmax of 1 h in plasma for both doses [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…In the pilot study mentioned in the Oil section, the subject received 100 mL of a cannabis decoction containing 0.36 mg of THC, 1.6 mg of THCA-A, 0.42 mg of CBD, and 4 mg of CBDA. This oral dose resulted in a Cmax in the serum of 1.0 ng/mL of THC and 72.4 ng/mL of THCA-A, with a Tmax of 2.0 h [ 53 ]. See Table 2 for the specific results.…”

Section: Resultsmentioning

confidence: 99%

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Oral Administration of Cannabis and Δ-9-tetrahydrocannabinol (THC) Preparations: A Systematic Review

et al. 2020

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Background and objective: Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms available, which are gaining popularity for both recreational and therapeutic use. From a therapeutic perspective, oral cannabis containing Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is a promising route of administration but there is still little information about its pharmacokinetics (PK) effects in humans. The purpose of this systematic review is to provide a general overview of the available PK data on cannabis and THC after oral administration. Materials and Methods: A search of the published literature was conducted using the PubMed database to collect available articles describing the PK data of THC after oral administration in humans. Results: The literature search yielded 363 results, 26 of which met our inclusion criteria. The PK of oral THC has been studied using capsules (including oil content), tablets, baked goods (brownies and cookies), and oil and tea (decoctions). Capsules and tablets, which mainly correspond to pharmaceutical forms, were found to be the oral formulations most commonly studied. Overall, the results reflect the high variability in the THC absorption of oral formulations, with delayed peak plasma concentrations compared to other routes of administration. Conclusions: Oral THC has a highly variable PK profile that differs between formulations, with seemingly higher variability in baked goods and oil forms. Overall, there is limited information available in this field. Therefore, further investigations are required to unravel the unpredictability of oral THC administration to increase the effectiveness and safety of oral formulations in medicinal use.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Oral Administration of Cannabis and Δ-9-tetrahydrocannabinol (THC) Preparations: A Systematic Review

et al. 2020

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A validated method for the simultaneous quantification of cannabidiol, Δ⁹‐tetrahydrocannabinol, and their metabolites in human plasma and application to plasma samples from an oral cannabidiol open‐label trial

Kevin

Vogel

Doohan

et al. 2020

Drug Testing and Analysis

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Cannabidiol (CBD) and Δ9‐tetrahydrocannabinol (THC) are the two best known and most extensively studied phytocannabinoids within Cannabis sativa. An increasing number of preclinical studies and clinical trials have been conducted with one or both compounds, often probing their therapeutic effects in conditions such as paediatric epilepsy, anxiety disorders or chronic pain. Accurate monitoring of THC and CBD and their metabolites is essential for tracking treatment adherence and pharmacokinetics. However, fully validated methods for the comprehensive analysis of major Phase I CBD metabolites are yet to be developed due to a historical lack of commercially available reference material. In the present study, we developed, optimised and validated a method for the simultaneous quantification of CBD, THC and their major Phase I metabolites 6‐hydroxy‐CBD (6‐OH‐CBD), 7‐hydroxy‐CBD (7‐OH‐CBD), 7‐carboxy‐CBD (7‐COOH‐CBD), 11‐hydroxy‐tetrahydrocannabinol (11‐OH‐THC) and 11‐carboxy‐tetrahydrocannabinol (11‐COOH‐THC) as per Food and Drug Administration (FDA) guidelines for bioanalytical method validation. The method is accurate, reproducible, sensitive and can be carried out in high‐throughput 96‐well formats, ideal for larger scale clinical trials. Deuterated internal standards for each analyte were crucial to account for variable matrix effects between plasma lots. The application of the method to plasma samples, taken from people who had been administered oral CBD as part of an open‐label trial of CBD effects in anxiety disorders, demonstrated its immediate utility in ongoing and upcoming clinical trials. The method will prove useful for future studies involving CBD and/or THC and can likely accommodate the inclusion of additional metabolites as analytical reference materials become commercially available.

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Progress in the analysis of phytocannabinoids by HPLC and UPLC (or UHPLC) during 2020–2023

Nahar,

Chaiwut,

Sangthong

et al. 2024

Phytochemical Analysis

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IntroductionOrganic molecules that bind to cannabinoid receptors are known as cannabinoids. These molecules possess pharmacological properties similar to those produced by Cannabis sativa L. High‐performance liquid chromatography (HPLC) and ultra‐performance liquid chromatography (UPLC, also known as ultra‐high‐performance liquid chromatography, UHPLC) have become the most widely used analytical tools for detection and quantification of phytocannabinoids in various matrices. HPLC and UPLC (or UHPLC) are usually coupled to an ultraviolet (UV), photodiode array (PDA), or mass spectrometric (MS) detector.ObjectiveTo critically appraise the literature on the application of HPLC and UPLC (or UHPLC) methods for the analysis of phytocannabinoids published from January 2020 to December 2023.MethodologyAn extensive literature search was conducted using Web of Science, PubMed, and Google Scholar and published materials including relevant books. In various combinations, using cannabinoid in all combinations, cannabis, hemp, hashish, C. sativa, marijuana, analysis, HPLC, UHPLC, UPLC, and quantitative, qualitative, and quality control were used as the keywords for the literature search.ResultsSeveral HPLC‐ and UPLC (or UHPLC)‐based methods for the analysis of phytocannabinoids were reported. While simple HPLC‐UV or HPLC‐PDA‐based methods were common, the use of HPLC‐MS, HPLC‐MS/MS, UPLC (or UHPLC)‐PDA, UPLC (or UHPLC)‐MS, and UPLC (or UHPLC)‐MS/MS was also reported. Applications of mathematical and computational models for optimization of protocols were noted. Pre‐analyses included various environmentally friendly extraction protocols.ConclusionDuring the last 4 years, HPLC and UPLC (or UHPLC) remained the main analytical tools for phytocannabinoid analysis in different matrices.

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Fast and sensitive UHPLC-MS/MS analysis of cannabinoids and their acid precursors in pharmaceutical preparations of medical cannabis and their metabolites in conventional and non-conventional biological matrices of treated individual

Cited by 42 publications

References 18 publications

Oral Administration of Cannabis and Δ-9-tetrahydrocannabinol (THC) Preparations: A Systematic Review

Oral Administration of Cannabis and Δ-9-tetrahydrocannabinol (THC) Preparations: A Systematic Review

A validated method for the simultaneous quantification of cannabidiol, Δ⁹‐tetrahydrocannabinol, and their metabolites in human plasma and application to plasma samples from an oral cannabidiol open‐label trial

Progress in the analysis of phytocannabinoids by HPLC and UPLC (or UHPLC) during 2020–2023

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Fast and sensitive UHPLC-MS/MS analysis of cannabinoids and their acid precursors in pharmaceutical preparations of medical cannabis and their metabolites in conventional and non-conventional biological matrices of treated individual

Cited by 42 publications

References 18 publications

Oral Administration of Cannabis and Δ-9-tetrahydrocannabinol (THC) Preparations: A Systematic Review

Oral Administration of Cannabis and Δ-9-tetrahydrocannabinol (THC) Preparations: A Systematic Review

A validated method for the simultaneous quantification of cannabidiol, Δ9‐tetrahydrocannabinol, and their metabolites in human plasma and application to plasma samples from an oral cannabidiol open‐label trial

Progress in the analysis of phytocannabinoids by HPLC and UPLC (or UHPLC) during 2020–2023

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A validated method for the simultaneous quantification of cannabidiol, Δ⁹‐tetrahydrocannabinol, and their metabolites in human plasma and application to plasma samples from an oral cannabidiol open‐label trial