Potency Analysis of Medical Marijuana Products from New York State

Lingyun Li, Bryan C. Duffy, Lorie A. Durocher, Mark A. Dittmar, Robert A. Acosta, Emily R. Delaney, Lei Li, Kenneth M. Aldous and David C. Spink

Cannabis and Cannabinoid Research,  Volume X, Number X, 2019
Mary Ann Liebert, Inc.

DOI: 10.1089/can.2018.0037

Abstract

Introduction : In the United States, medicalmarijuana programs have been established in 29 states and the District of Columbia. In 2014, New York State (NYS) approved medical marijuana legislation, and its program became fully operational in January of 2016. Products manufactured under the auspices of the program may be used by certified patients in NYS for the treatment of 1 of 12 qualifying medical conditions. The NYS statute requires rigorous testing of each product lot manufactured in the state for its cannabinoid profile, bacterial and fungal contamination, mycotoxins, heavy metals, plant-growth regulators, and pesticides. Here, we report on the analysis of product cannabinoid profiles.

Methods : A method employing a simple extraction/dilution technique and reversed-phase high performance liquid chromatography with photodiode array detection (HPLC-PDA) was developed for the analysis of 10 cannabinoids: cannabidiolic acid, cannabigerolic acid, cannabigerol, cannabidiol (CBD), tetrahydrocannabivarin, cannabinol, D9-tetrahydrocannabinol (D9-THC), cannabichromene, cannabidivarin, and D9-tetrahydrocannabinolic acid-A. The method employed internal standard quantitation and incorporated a surrogate to monitor extraction efficiency and analytical recovery.

Results : The HPLC-PDA method was validated using sample matrices composed of medium-chain triglycerides, hemp oil, sesame oil, and an ethanol-propylene glycol tincture. Limits of detection, limits of quantitation, accuracy, precision, and inter- and intraday reproducibility were found to be highly satisfactory. The validated method has been used to analyze over 3500 samples from over 700 lots of medical marijuana products manufactured in NYS from January 2016 through April 2018. Quality control data showed quantitative spike recoveries and, for the analysis of samples from the same lot, the coefficients of variation for the principal analytes, D9-THC and CBD, averaged <3%. Using the HPLC PDA method, the NYS medical marijuana products were analyzed to verify the potencies on the product labels and to determine the stability of the products.

Conclusions : An HPLC-PDA-based method was developed, validated, and employed to analyze 10 cannabinoids in a variety of medical marijuana products. The method has proven to be accurate, precise, stable, and very robust. Its use is an integral part of the NYS Medical Marijuana program for validation of the content and consistency of medical marijuana products.

Keywords : D9-tetrahydro-cannabinol; cannabidiol; cannabinoids; HPLC; medical marijuana; potency analysis

 

Introduction

The use of cannabis in the treatment of human disease dates to at least 4000 BCE.1,2 Due to the purported and established beneficial effects of cannabis in the treatment of numerous conditions,3–6 there have been increased research and development efforts into cannabinoid-based drugs. At the federal level, the Food and Drug Administration (FDA) has approved two tetrahydrocannabinol-based medications, dronabinol, the active ingredient of which is synthetic D9-tetrahydrocannabinol (D9-THC), and nabilone, a semisynthetic analog of D9-THC.7 These drugs are used to treat cancer patients undergoing chemotherapy who have nausea and vomiting that is not adequately controlled by conventional antiemetic treatments and for anorexia associated with weight loss in patients with AIDS. Recently, the FDA approved epidiolex, a formulation of purified cannabidiol (CBD), for the treatment of two rare and severe forms of epilepsy.8 In parallel developments at the state level, medical marijuana programs have been initiated in 29 states in the United States and the District of Columbia.9 An additional 17 states have established CBD-only programs. Since the state-operated medical marijuana and CBD-only programs are not under the purview of the FDA, it is the responsibility of the individual states to determine whether and how to monitor the potency of the products and their potential microbial and chemical contamination.

In July 2014, New York State (NYS) approved medical marijuana legislation, and its program became fully operational in January 2016. Medical marijuana is currently permitted in NYS for the treatment of conditions including amyotrophic lateral sclerosis, cancer, epilepsy, HIV/AIDS, Huntington’s disease, inflammatory bowel disease, Parkinson’s disease, post-traumatic stress disorder, multiple sclerosis, neuropathies, spinal cord injuries associated with spasticity, and chronic pain.10 The NYS program disallows the smoking of cannabis, but a variety of cannabis products including capsules, oils, tinctures, and vaporizer cartridges are available. The NYS regulations on medical marijuana require rigorous testing of each final product lot produced in the state for its cannabinoid profile, bacterial and fungal contamination, mycotoxins, heavy metals, plant-growth regulators, and pesticides. The Medical Marijuana Laboratory of the Wadsworth Center has developed, validated, and employed methods for each of these required tests.Methods using high-performance liquid chromatography with photodiode-array detection (HPLC-PDA) have proven effective for the determination of cannabinoids in cannabis plant material,11–13 and thus served as a basis for our procedures for the analysis of medical marijuana products.

This initial article from the Wadsworth Center Medical Marijuana Laboratory reports on the development and validation of methods for the extraction and analysis of cannabinoids in CO2 extract-based medical marijuana products using HPLC-PDA. We further report on the performance of our method in the analysis of over 700 lots of medical marijuana products during the first 2 years of the NYS Medical Marijuana Program and on stability studies of opened and unopened products.

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