s41598-022-23910-6.pdf (1.6 MB)
The reported characteristics of cannabidiol (CBD) have encouraged significant growth in commercial CBD products. There is limited information on the stability of CBD and some researchers have noted significant reductions of CBD in products. In this study, the chemical profiles of plant-based and chemically synthesized CBD in a prototype e-liquid formulation were assessed during 4 weeks of storage under varying conditions. Samples were analysed on days 1, 8, 15, 22, and 29 by untargeted analysis using ultra-high performance liquid chromatography—trapped ion mobility–time-of-flight mass spectrometry (UHPLC-TIMS-TOF-MS). On day 1, analysis of plant-based and synthetic CBD formulations showed small differences in their composition, with plant-based CBD e-liquid containing trace levels of a higher number of phytocannabinoid-related impurities. Storage for 4 weeks under stress (40 °C, 75% relative humidity, dark) and ambient (25 °C, 60% relative humidity, daylight) conditions led to increases in the number and abundance of cannabinoid-related degradation products, including cannabielsoin (CBE) and CBD-hydroxyquinone (HU-331), which are products of the oxidation of CBD, and other unidentified cannabinoid-related compounds. The unidentified cannabinoid-related compounds were probed by accurate mass measurement and MS2 fragmentation but could not be matched using a mass spectral library derived from 39 commercially available cannabinoid reference standards. Based on elemental composition and MS2 fragmentation patterns, the unidentified cannabinoid-related compounds were classified as hydroxy-CBE, hydroxy-CBD, and dihydroxy-CBD. The analysis of e-liquid formulations protected from light and stored at 4 °C for 4 weeks indicated only very small increases in CBD oxidation products. The results indicate that CBD degrades in e-liquid solution at ambient temperature in dark and light to form potentially undesirable products, including cannabielsoin and cannabidiol hydroxyquinone.
Formulation and storage of CBD e-liquids
To characterise impurities associated with plant-based and synthetic CBD in e-liquid formulations stored under different conditions, two unflavoured, non-commercial CBD e-liquids were prepared by adding either CBD isolate (60 mg/mL) or synthetic CBD (60 mg/mL) to a mixture of pharmaceutical-grade propylene glycol (70%) and pharmaceutical-grade glycerol (30%).
Who cuts their meds from 800mg/ml down to 60mg/ml before huffing it?
If huffing stuff ain’t good, why huff 10x more to get your damn dose?!?
This is exactly what pharma does though. They give you an inhaler (like sativax) that each dose is just 10mg in the spray. Similar with the dosing of epidilex. Its kind of always been that way due to the stability and strange dosing requirements of the regulations at the FDA.
Its like this - if you have basically nothing in a dose, then if it degrades in a miniscule amount, you are still below the legal threshold of impurities (yes, its defined, we could look it up if we wanted…)
If you have a concentrated solution instead, then if it degrades in a miniscule amount, you are now above the legal threshold for impurities and voila now you must identify all of them, track all of them, test them all, include them in your CMC package, and continue to monitor for them for the rest of the drugs lifetime on the commercial market as part of the monograph.
Cannot tell you how many times I have formulated things IN OTHER THINGS just so they would appear to be more stable. Or added lots of OTHER THINGS just to make them more stable. Or to make them pass a dissolution test. Or to make them pass an impurities test. Its like crazy how these things are done.
There are also weird things like this done for taste profiles. And there are weird things done like this to make the dosage form get to the right place (like coatings to bypass the stomach and make it into the intestines for instance…)
Anyway - cool article/study. We have kind of known this stuff for a while now - its nice to see they are at least attempting to quantify and identify some of the degradation products now. 
HU-331 as a degradation compound.
Spicy.