LC–MS/MS quantitation of phytocannabinoids and their metabolites in biological matrices

Abd-Elsalam, Wessam H.; Alsherbiny, Muhammad A.; Kung, Janice Y.; Pate, David W.; Löbenberg, Raimar

doi:10.1016/j.talanta.2019.06.053

Cited by 33 publications

(13 citation statements)

References 127 publications

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“…The current legal status of CBD is neither clear nor harmonised worldwide, although there are widespread medicinal, food, or cosmetic products that contain CBD [ 21 , 22 ]. Intriguingly, liquid chromatography coupled with mass spectrometry enables the subnanomolar detection and quantitation of cannabinoids in different biological matrices [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms

Alsherbiny

Bhuyan

Low

et al. 2021

IJMS

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Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has recently emerged as a potential cytotoxic agent in addition to its ameliorative activity in chemotherapy-associated side effects. In this work, the potential interactions of CBD with docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-ethyl-10-hydroxycamptothecin (SN−38) were explored in MCF7 breast adenocarcinoma cells using different synergy quantification models. The apoptotic profiles of MCF7 cells after the treatments were assessed via flow cytometry. The molecular mechanisms of CBD and the most promising combinations were investigated via label-free quantification proteomics. A strong synergy was observed across all synergy models at different molar ratios of CBD in combination with SN−38 and VIN. Intriguingly, synergy was observed for CBD with all chemotherapeutic drugs at a molar ratio of 636:1 in almost all synergy models. However, discording synergy trends warranted the validation of the selected combinations against different models. Enhanced apoptosis was observed for all synergistic CBD combinations compared to monotherapies or negative controls. A shotgun proteomics study highlighted 121 dysregulated proteins in CBD-treated MCF7 cells compared to the negative controls. We reported the inhibition of topoisomerase II β and α, cullin 1, V-type proton ATPase, and CDK-6 in CBD-treated MCF7 cells for the first time as additional cytotoxic mechanisms of CBD, alongside sabotaged energy production and reduced mitochondrial translation. We observed 91 significantly dysregulated proteins in MCF7 cells treated with the synergistic combination of CBD with SN−38 (CSN−38), compared to the monotherapies. Regulation of telomerase, cell cycle, topoisomerase I, EGFR1, protein metabolism, TP53 regulation of DNA repair, death receptor signalling, and RHO GTPase signalling pathways contributed to the proteome-wide synergistic molecular mechanisms of CSN−38. In conclusion, we identified significant synergistic interactions between CBD and the five important chemotherapeutic drugs and the key molecular pathways of the combination of CBD and CSN−38 in MCF7 cells. Further in vivo and clinical studies are warranted to evaluate the implementation of CBD-based synergistic adjuvant therapies for breast cancer.

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Section: Introductionmentioning

confidence: 99%

Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms

Alsherbiny

Bhuyan

Low

et al. 2021

IJMS

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“… 14 With superior high sensitivity and specificity, liquid chromatography–tandem mass spectrometry (LC–MS/MS) is able to detect tiny variations in the intensity of metabolites and thus is widely being used in metabonomics research. 15 By using LC–MS, metabolomics analysis was conducted in previous studies to explore the metabolic abnormalities in the lung tissue 5 or the RV tissue of PAH. 16 However, the pathogenesis of PAH varies in different categories.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Reprogramming of the Right Ventricle and Pulmonary Arteries in a Flow-Associated Pulmonary Arterial Hypertension Rat Model

Liu

Qin

et al. 2021

ACS Omega

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Pulmonary arterial hypertension (PAH) is a complex devastating disease relevant to remarkable metabolic dysregulation. Although various research studies on PAH from a metabolic perspective have been emerging, pathogenesis of PAH varies in different categories. Research on metabolic reprogramming in flow-associated PAH remains insufficient. An untargeted metabolomic profiling platform was used to evaluate the metabolic profile of pulmonary arteries (PAs) as well as the right ventricle (RV) in a flow-associated PAH rat model in the present work. A total of 79 PAs and 128 RV metabolites were significantly altered in PAH rats, among which 39 metabolites were assessed as shared dysregulated metabolites in PAs and the RV. Pathway analysis elucidated that, in PAs of PAH rats, pathways of phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism were significantly altered, while in the RV, arginine biosynthesis and linoleic acid metabolism were altered dramatically. Further integrated analysis of shared dysregulated PA and RV metabolites demonstrated that the linoleic acid metabolism and the arachidonic acid (AA) metabolism were the key pathways involved in the pathogenesis of flow-associated PAH. Results obtained from the present work indicate that the PAH pathogenesis could be mediated by widespread metabolic reprogramming. In particular, the dysregulation of AA metabolism may considerably contribute to the development of high blood flow-associated PAH.

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“…For the development of LC-MS/MS, the chromatographic separation and ESI condition were investigated based on previous reports. 9,10 Usually, the unexceptional LC…”

Section: Resultsmentioning

confidence: 99%

Screening Method for the Quality Evaluation of Cannabidiols in Water-based Products Using Liquid Chromatography Tandem Mass Spectrometry

et al. 2020

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A sensitive, useful and preliminary screening method was proposed to quantitate the containable cannabinoids most commonly included in mineral water and gummi candy products, specifically cannabidiol (CBD), cannabinol (CBN), 11-nor-9-carboxy-Δ 9tetrahydrocannabinol (THCA), cannabigerol (CBG), and cannabidiolic acid (CBDA), using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for the quality evaluation. Based on the electrospray positive ion mode, the limit of detection and limit of quantification values were 0.2 to 0.5 ng/mL and 0.8 and 2.0 ng/mL. Samples (0.5 g) were diluted by water/methanol (50/50), to which stable isotope internal standards were added, and the recovery results were shown in range from 91.3 to 101.2%. This method was applied to evaluate the CBD products (6 kinds) from Japanese market. Our survey found obvious discrepancies between the labeling and the results we overserved in products. In addition, CBN, THCA, CBG, and CBDA were not detected in full spectrum products that contain various cannabinoids that are naturally occurring in the cannabis plant. Thus, it is necessary to be able to verify the accurate concentration and impurity in various CBD products from Japanese market as quickly as possible.

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LC–MS/MS quantitation of phytocannabinoids and their metabolites in biological matrices

Cited by 33 publications

References 127 publications

Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms

Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms

Metabolic Reprogramming of the Right Ventricle and Pulmonary Arteries in a Flow-Associated Pulmonary Arterial Hypertension Rat Model

Screening Method for the Quality Evaluation of Cannabidiols in Water-based Products Using Liquid Chromatography Tandem Mass Spectrometry

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