Evaluation of long-term stability of cannabinoids in standardized preparations of cannabis flowering tops and cannabis oil by ultra-high-performance liquid chromatography tandem mass spectrometry

Roberta Pacifici; Emilia Marchei; Francesco Salvatore; Luca Guandalini; Francesco Paolo Busardò; Simona Pichini

doi:10.1515/cclm-2017-0758

Requires Authentication Published by De Gruyter November 27, 2017

Evaluation of long-term stability of cannabinoids in standardized preparations of cannabis flowering tops and cannabis oil by ultra-high-performance liquid chromatography tandem mass spectrometry

Roberta Pacifici
Roberta Pacifici
National Centre on Addiction and Doping, Istituto Superiore di Sanità, V.le Regina Elena 299, 00161, Rome, Italy, Phone: +390649906544, Fax: +390649902016

Email author

Search for this author in:

De Gruyter | Google Scholar
, Emilia Marchei
Emilia Marchei
National Centre on Addiction and doping, Istituto Superiore di Sanità, Rome, Italy

Search for this author in:

De Gruyter | Google Scholar
, Francesco Salvatore
Francesco Salvatore
Agenzia Industrie e Difesa, Stabilimento Chimico Farmaceutico Militare; (Military Pharmaceutical Chemical Works of Florence), Florence, Italy

Search for this author in:

De Gruyter | Google Scholar
, Luca Guandalini
Luca Guandalini
Agenzia Industrie e Difesa, Stabilimento Chimico Farmaceutico Militare; (Military Pharmaceutical Chemical Works of Florence), Florence, Italy

Search for this author in:

De Gruyter | Google Scholar
, Francesco Paolo Busardò
Francesco Paolo Busardò
Unit of Forensic Toxicology (UoFT), Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy

Search for this author in:

De Gruyter | Google Scholar
and Simona Pichini
Simona Pichini
National Centre on Addiction and doping, Istituto Superiore di Sanità, Rome, Italy

Search for this author in:

De Gruyter | Google Scholar

From the journal Clinical Chemistry and Laboratory Medicine (CCLM)

https://doi.org/10.1515/cclm-2017-0758

You are currently not able to access this content.
Not sure if you should have access? Please log in using an institutional account to see if you have access to view or download this content.
For more information see https://www.degruyter.com/how-access-works

Showing a limited preview of this publication:

Clin Chem Lab Med 2018; 56(4): e94–e96Letter to the EditorRoberta Pacifici*, Emilia Marchei, Francesco Salvatore, Luca Guandalini, Francesco Paolo Busardò and Simona PichiniEvaluation of long-term stability of cannabinoids in standardized preparations of cannabis flowering tops and cannabis oil by ultra-high-performance liquid chromatography tandem mass spectrometryhttps://doi.org/10.1515/cclm-2017-0758Received August 25, 2017; accepted September 21, 2017; previously published online November 27, 2017Keywords: medical cannabis; stability; ultra-high- performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS).To the Editor,From November 2015, Italy started autonomous cultiva-tion and production of medical cannabis, authorized by a Decree of the Italian Ministry of Health [1]. From January 2017, the batches of Cannabis FM2, a cannabis with stand-ardized amount of 6.5% (w/w) Δ-9-tetrahydrocannabinol (THC) and 8% (w/w) cannabidiol (CBD) manufactured by the Military Pharmaceutical Chemical Works of Florence, came into the market.In order to guarantee the quality and the tempo-ral inalterability of cannabis preparations and conse-quently therapeutic continuity in individuals treated with medical cannabis, the Italian National Institute of Health, as indicated in the Ministerial Decree, was com-mitted to evaluate cannabinoid concentration and stabil-ity in standardized preparations of cannabis flowering tops, cannabis tea and oil.In this concern, we recently evaluated cannabinoid content in the first 10 batches of FM2 and cannabinoid concentration and short-term (up to 14 days) stability in standardized preparations of cannabis tea and cannabis oil [2]. We showed that the 10 different batches of flow-ering tops effectively contained a mean 5.8% THC and a mean 8.1% CBD with minimal variations between batches and that cannabinoid stability in aqueous solution was so short that extemporaneous tea preparation was rec-ommended, whereas in case of oil preparation, a loss of around 20% initial concentration was observed for all the studied cannabinoids for the first 14 days of storage.It has been shown that cannabinoid content in can-nabis plant and in its products (e.g. resin and hashish oil) fall as storage time increase in terms of months and years [3–6]. Nevertheless, up to now, no data are available for long-term stability of cannabis flowering tops and medical cannabis oil.Taking all this into account, the Italian National Insti-tute of Health, in agreement with the Health Commis-sion on Medical Cannabis and Military Pharmaceutical Chemical Works of Florence, aimed to evaluate the 1-year stability of cannabinoids in standardized preparations of cannabis flowering tops and cannabis oil by the ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay, developed and vali-dated in the previous study [2].We measured the content (% w/w) of THC, Δ9-tetrahydrocannabinolic acid A (THCA-A), CBD, canna-bidiolic acid (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC) in the 10 batches of FM2 cannabis, previously used to study short-term stability [2], stored inside closed plastic containers in darkness at room temperature (about 25 °C) and in six different repli-cates of cannabis oil, prepared as previously described [2] and stored in darkness at 4 °C. In the specific case of oil, no oven preheating was performed, which decarboxylated THCA-A and CBDA to THC and CBD, respectively, prevent-ing the stability study of acidic compounds over the time.In case of FM2, the 1-year storage of cannabis at ambient temperature caused only slight changes in the *Corresponding author: Roberta Pacifici, National Centre on Addiction and Doping, Istituto Superiore di Sanità, V.le Regina Elena 299, 00161, Rome, Italy, Phone: +390649906544, Fax: +390649902016, E-mail: roberta.pacifici@iss.itEmilia MarcheiandSimona Pichini: National Centre on Addiction and doping, Istituto Superiore di Sanità, Rome, ItalyFrancesco SalvatoreandLuca Guandalini: Agenzia Industrie e Difesa, Stabilimento Chimico Farmaceutico Militare; (Military Pharmaceutical Chemical Works of Florence), Florence, ItalyFrancesco Paolo Busardò: Unit of Forensic Toxicology (UoFT), Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy

Keywords: medical cannabis; stability; ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS)

Acknowledgments

The authors thank Stefano Gentili, Michele Sciotti, Simonetta di Carlo, Antonella Bacosi and Laura Martucci for their technical assistance.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Funded by the project: “Implementazione dei Sistemi di Sorveglianza sul disturbo da gioco d’azzardo e sull’uso medico della cannabis sul territorio Nazionale” by the Ministry of Health.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Decreto 9 novembre 2015: Funzioni di Organismo statale per la cannabis previsto dagli articoli 23 e 28 della convenzione unica sugli stupefacenti del 1961, come modificata nel 1972. Available at: http://www.gazzettaufficiale.it/eli/id/2015/11/30/15A08888/sg;jsessionid=p1rnwNujUKlqQ5azhAQ95A__.ntc-as3-guri2a. Accessed: 24 Aug 2017.Search in Google Scholar

2. Pacifici R, Marchei E, Salvatore F, Guandalini L, Busardò FP, Pichini S. Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry. Clin Chem Lab Med 2017;55:1555–63. [Epub ahead of print].10.1515/cclm-2016-1060Search in Google Scholar PubMed

3. Trofin IG, Dabija G, Váireanu DI, Filipescu L. The influence of long-term storage conditions on the stability of cannabinoids derived from cannabis resin. Rev Chim 2012;63:422–7.Search in Google Scholar

4. Trofin IG, Dabija G, Váireanu DI, Filipescu L. Long term storage and cannabis oil stability. Rev Chim 2012;63:293–7.Search in Google Scholar

5. Taschwer M, Schmid MG. Determination of the relative percentage distribution of THCA and Δ(9)-THC in herbal cannabis seized in Austria – Impact of different storage temperatures on stability. Forensic Sci Int 2015;254:167–71.10.1016/j.forsciint.2015.07.019Search in Google Scholar PubMed

6. Lindholst C. Long term stability of cannabis resin and cannabis extracts. Australian J Forensic Sci 2010;42:181–90.10.1080/00450610903258144Search in Google Scholar

7. Rock EM, Limebeer CL, Parker LA. Effect of combined doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague-Dawley) models of conditioned gaping. Psychopharmacology 2015;232:4445–4.10.1007/s00213-015-4080-1Search in Google Scholar PubMed

8. Brierley DI, Samuels J, Duncan M, Whalley BJ, Williams CM. Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea. Psychopharmacology 2016;233:243–54.10.1007/s00213-015-4100-1Search in Google Scholar PubMed

9. Carbone M, Castelluccio F, Daniele A, Sutton A, Ligresti A, Di Marzo V, et al. Chemical characterisation of oxidative degradation products of Δ9-THC. Tetrahedron 2010;66:9497–501.10.1016/j.tet.2010.10.025Search in Google Scholar

Received: 2017-8-25

Accepted: 2017-9-21

Published Online: 2017-11-27

Published in Print: 2018-3-28

— or —

PDF $42.00

Buy Article

From the journal

Clinical Chemistry and Laboratory Medicine (CCLM)

Volume 56 Issue 4

Journal and Issue

Articles in the same Issue

Frontmatter

Editorial

Visual assessment of sample quality: quo usque tandem?

Reviews

Machine learning in laboratory medicine: waiting for the flood?

Is irisin the new player in exercise-induced adaptations or not? A 2017 update

Opinion Paper

Can a combination of average of normals and “real time” External Quality Assurance replace Internal Quality Control?

Genetics and Molecular Diagnostics

The UGT1A1*28 gene variant predicts long-term mortality in patients undergoing coronary angiography

General Clinical Chemistry and Laboratory Medicine

Laboratory performance of sweat conductivity for the screening of cystic fibrosis

Making sense of a haemolysis monitoring and reporting system: a nationwide longitudinal multimethod study of 68 Australian laboratory participant organisations

Visual assessment of hemolysis affects patient safety

Strong impact on plasma protein profiles by precentrifugation delay but not by repeated freeze-thaw cycles, as analyzed using multiplex proximity extension assays

Validation of the Six Sigma Z-score for the quality assessment of clinical laboratory timeliness

Proficiency testing program for hemoglobin E, A₂ and F analysis in Thailand using lyophilized hemoglobin control materials

Application of κ free light chains in cerebrospinal fluid as a biomarker in multiple sclerosis diagnosis: development of a diagnosis algorithm

Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential diagnostic markers and risk predictors of venous thrombosis and obstetric complications in antiphospholipid syndrome

An evaluation of the SENTiFIT 270 analyser for quantitation of faecal haemoglobin in the investigation of patients with suspected colorectal cancer

Evaluation of the Aptima HBV Quant assay vs. the COBAS TaqMan HBV test using the high pure system for the quantitation of HBV DNA in plasma and serum samples

Reference Values and Biological Variations

Reference intervals for stone risk factors in 24-h urine among healthy adults of the Han population in China

Cardiovascular Diseases

Rule-out of non-ST elevation myocardial infarction by five point of care cardiac troponin assays according to the 0 h/3 h algorithm of the European Society of Cardiology

Infectious Diseases

Diagnostic and prognostic value of presepsin vs. established biomarkers in critically ill patients with sepsis or systemic inflammatory response syndrome

Association of adrenal hormone metabolites and mortality over a 6-year follow-up in COPD patients with acute exacerbation

Corrigendum

Corrigendum to: Validation of a pneumatic tube system to transport surgical pathology biopsy samples

Letters to the Editor

A transnational collaborative network dedicated to the study and applications of the vascular endothelial growth factor-A in medical practice: the VEGF Consortium

Detection and a functional characterization of the novel FBN1 intronic mutation underlying Marfan syndrome: case presentation

Effect of haemolysis on the determination of CCL17/thymus and activation-regulated chemokine (TARC) and CCL22/macrophage-derived chemokine (MDC)

Evaluation of long-term stability of cannabinoids in standardized preparations of cannabis flowering tops and cannabis oil by ultra-high-performance liquid chromatography tandem mass spectrometry

Impact of citrated blood collection tubes on red cell morphology: implications for the measurement of plasma glucose

Validation of a pneumatic tube system to transport surgical pathology biopsy samples

Antioxidant capacity in patients with type 2 diabetes: a preliminary investigation on gender-specific differences in an Italian population