Potency Testing by LC-MS, the Future of Cannabinoid Testing?

Potency testing is the bread and butter of the cannabis industry. This analysis is typically performed by LC-UV as this instrumentation is relatively inexpensive and requires minimal training. There are over 150 cannabinoids that have been discovered thus far, with more likely to be discovered in the coming years as cannabis research continues to accelerate. While LC-UV is a robust and reliable approach, it has some limitations. LC-UV is hindered by the need to resolve all analytes and lacks sensitivity when compared to MS. As new cannabinoids are discovered and gain interest, additional cannabinoids will need to be added into potency testing methods. MS can offer a sensitive and selective analytical solution which enables lower limits of detection and eliminates the need to resolve compounds that are not isobars. Here, a method has been developed for the analysis of 21 cannabinoids by LC-MS in 9 minutes that also achieves the resolution of all isobaric compounds.

Column	Raptor ARC-18 (cat.#9314A62)
Dimensions:	150 mm x 2.1 mm ID
Particle Size:	2.7 µm
Guard Column:	Raptor ARC-18 EXP guard column cartridge 2.7 µm (cat.#9314A0252)
Temp.:	30 °C
Conc.:	500 ppb
Inj. Vol.:	2 µL
Mobile Phase
A:	Water, 0.1% formic acid
B:	Acetonitrile & Methanol 50/50, 0.1% formic acid
Time (min)	Flow (mL/min)	%B
0	0.5	80
0.9	0.5	80
Ion Mode	ESI (+)/(-)
Detector	MS

 

Peaks	SIM	Ion Mode
Cannabidivarin	287	+
Cannabidivarinic Acid	331	+
Cannabidiol	315	+
Cannabigerol	317	+
Cannabidiolic Acid	357	-
Tetrahydrocannabivarin	287	+
Cannabigerolic Acid	359	-
Cannabichromevarin	287	+
Cannabinol	311	+
Cannabidiphorol	343.5	+
Tetrahydrocannabivarinic Acid	331	+
Δ9-Tetrahydrocannabinol	315	+
Δ8-Tetrahydrocannabinol	315	+
Cannabinolic Acid	353	-
Cannabicyclol	315	+
Cannabichromene	315	+
Tetrahydrocannabinolic Acid-A	357	-
Cannabicitran	315	+
Tetrahydrocannabiphorol	343.5	+
Cannabichromenic Acid	357	-
Cannabicyclolic acid	357	-

In the above compound table, each analyte is listed with their SIM and ESI ion mode. All isobars are color coded and these compounds will need to be chromatographically separated.

In this method, 21 cannabinoids are capable of being analyzed by LC-MS. By using MS detection, some of the burden is lifted to chromatographically separate all compounds, as only isobars need to be separated. Some of the isobars are more difficult to separate than others. The most challenging set to separate are the m/z of 315, which consists of THC and its isobars.

By using this method, the desired resolution can be achieved for key compounds, including THC isobars. Additional cannabinoids can be added to the analyte list as more are discovered with minimal further optimization. Could MS be the future of cannabinoid potency testing?