Methods for Testing Cannabis Potency: Understanding HPLC, GC-MS, and LC-MS

Potency testing measures cannabinoids such as THC and CBD. It’s the number consumers shop by and the number on the label, so it has to be right. This post compares the three instruments used for it, HPLC, GC-MS and LC-MS: how they work, where each is strong and weak, and which one suits which job.

HPLC

High-performance liquid chromatography (HPLC) separates cannabinoids between a liquid mobile phase and a stationary phase. It’s sensitive, accurate and reproducible, which makes it the preferred method for potency. It also leaves the acid forms of the cannabinoids intact, so THCA and CBDA are measured directly instead of being converted on the way in (7 CFR 990.1).

In California the method is no longer each lab’s choice. Every licensed lab has to run the state’s standard HPLC method for dried flower and non-infused pre-rolls, and has had to since January 1, 2024 (Cal. Code Regs. tit. 4, §15712.1).

HPLC seems to me to be the litmus test for whether a laboratory is working well. If you can find a method, enter the parameters, make the system behave and interpret the results it produces, you can probably do the same for every other instrument in the lab with a little elbow grease.

GC-MS

Gas chromatography-mass spectrometry (GC-MS) separates compounds in a gas mobile phase and identifies them by their mass spectra. It’s sensitive and specific, and it can detect and quantify trace amounts of cannabinoids.

The catch for potency is heat. The hot GC inlet converts THCA into THC, so a GC result is total THC, not the acid and the neutral form reported separately. USDA’s hemp rule describes exactly this conversion (7 CFR 990.1).

A GC with a flame ionization detector (GC-FID) also works for residual solvents. In my experience, GC-MS is best used for terpenes. When it works, it works: samples go in and results come out without much fuss. Getting it to work in the first place is the trick.

Terpene testing is usually optional. California tests terpenoids only when a client asks (tit. 4, §15725), while Nevada lists terpene analysis among the required tests for flower (NCCR 11.050). For how requirements shift over time, read our post on the evolution of testing regulations.

LC-MS

Liquid chromatography-mass spectrometry (LC-MS) couples the separation of HPLC with the detection of mass spectrometry. It’s sensitive and specific enough to quantify cannabinoids in complex matrices. It also takes a complex setup and expensive equipment, which is frustrating, because pesticide analysis should, in my opinion, stay standard in cannabis testing.

That said, we have yet to come across a functioning LC-MS system that we couldn’t get to work (we don’t repair broken hardware). Tell us about your LC-MS problems. I have a theory that most laboratories have some.

Choosing the right method

The choice depends on the accuracy, sensitivity and specificity you need, and on the budget and expertise you have.

• HPLC is the method for high-throughput potency testing: sensitive, reproducible, and it reports THCA and THC separately.
• GC-FID suits residual solvents, and GC-MS suits terpenes.
• LC-MS/MS offers high sensitivity and specificity and, in my experience, is best suited to pesticides.

Those are usually the big three. Heavy metals, run by ICP-MS, bring their own challenges, and whether they’re required depends on the state: California requires them on every sample (tit. 4, §15723), while Washington requires them only for its Department of Health-compliant products (WAC 314-55-102). pH and water activity need little method development: those instruments are simple out of the box.

Potency testing is what makes a label accurate and lets people use cannabis products knowingly. Each instrument has strengths and weaknesses, so choose by the analyte, the matrix and your state’s rules. When a method won’t validate or an instrument won’t hold its calibration, that’s the work behind Instruments & methods.