GC-MS failed to distinguish between CBD and THC

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Rkamer

GC-MS failed to distinguish between CBD and THC

Post by Rkamer » Wed Oct 16, 2019 11:10 am

The NY Times just published an article stating:
https://www.nytimes.com/2019/10/15/scie ... on=Science

"The drug testing method in question involves a common chemical analysis device called a gas-chromatography mass-spectrometry, or GC-MS, machine. Most such devices require the drug testing lab to add a chemical to a sample in order to identify trace amounts of illicit compounds, in a process called derivatization. Labs can perform derivatization using a variety of chemical agents, but one of the most common is called trifluoroacetic anhydride, or TFAA.
According to the 2012 journal article, TFAA when used by a GC-MS machine was unable to discern between CBD and THC. If a person who used only CBD were given a drug test that employed this device, method and chemical, the results would falsely report the presence of THC."

What is your take on this? How can we be sure our labs are using acceptable methods to avoid this problem?

Thanks



Robert Swotinsky MD
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Re: GC-MS failed to distinguish between CBD and THC

Post by Robert Swotinsky MD » Wed Oct 16, 2019 6:52 pm

The 2012 Journal of Analytical Toxicology article referenced in the NY Times article describes conversion of CBD to THC when incubated w/acid, heat, and time. This phenomenon has been described in other studies, too. The article does not describe the GC/MS being unable to distinguish between CBD and THC, except to the extent that CBD may be chemically converted to THC w/acid, heat, and time.

NLCP issued a notice to laboratories on May 28, 2019, about this as follows:
__________

NLCP Notice May 28, 2019

Attention: HHS-Certified and Applicant Laboratories and NLCP Inspectors

Subject: Possible Conversion of 7-carboxy-cannabidiol (CBDA) to 11-nor-9-carboxy- tetrahydrocannabinol (THCA) during Confirmatory Testing

The National Laboratory Certification Program (NLCP) is alerting HHS certified laboratories to the possibility of conversion of the cannabidiol (CBD) metabolite 7 carboxy cannabidiol (CBDA) to 11 nor 9 carboxy tetrahydrocannabinol (THCA) when an acidic derivatizing reagent is used during extraction for GC MS confirmatory testing.

Specimen Investigation

This issue was identified during an investigation into a retest specimen that failed to reconfirm for THCA. As shown in the table below, the A laboratory used an acidic derivatizing reagent (HFIP/HFBA) for the original analysis and for reanalysis during the investigation. Two other laboratories (one using a non acidic derivatizing agent; one using LC-MS/MS) did not detect THCA in the A and B specimens. The A laboratory changed their THCA assay to use a non acidic derivatizing reagent (BSTFA) and did not detect THCA when the specimen was analyzed using the new assay. All three laboratories tested the A and/or B specimens using the same THCA immunoassay kit (ThermoFisher DRI) and obtained positive initial test results.


Lab.............................Analysis Month (2018).....THCA Result......Derivatizing reagent
A lab (A bottle)...............June .........................76 ng/mL.........HFIP/HFBA
A lab (A bottle)...............August.......................73 ng/mL.........HFIP/HFBA
B lab (B bottle)...............July...........................ND................BSTFA
B lab (aliquot of A)...........September...................ND................BSTFA
C lab (aliquots of A and B)...December...................ND................None (LC-MS/MS)
A lab (A bottle)................January 2019...............ND................BSTFA

Investigation of THCA Initial and Confirmatory Methods Used in HHS-Certified Laboratories

The NLCP directed additional testing of this THCA negative specimen as well as some CBD dosing study samples at multiple HHS certified laboratories. The study samples were known to contain CBD and metabolites, and no THCA.

Based on the investigation to date:

• The THCA negative specimen tested positive using the Thermofisher DRI and the Roche KIMS THCA immunoassays. It appears that a substance other than THCA, possibly CBDA,cross-reacts with these immunoassays.
• The Siemens EMIT II THCA immunoassay does not appear to have sufficient cross-reactivity to CBD and metabolites to cause a positive result. Study samples containing CBD and metabolites, with no THCA, tested negative with this immunoassay.
• Eight study samples were tested using a GC MS assay with an acidic derivatizing reagent (PFAA and PFPOH):
o In 3 of the 8 samples: THCA was present above the limit of quantification (LOQ) but below the cutoff.
o The other 5 samples were negative for THCA.
• The same laboratory tested the same eight study samples using a non acidic derivatizing reagent (iodopropane) and did not detect THCA above the LOQ in any of the samples.

Future Program Actions

The NLCP is in the process of obtaining a CBDA standard. After obtaining this standard, the NLCP plans to send a special CBDA/THCA Performance Test (PT) set to all HHS certified laboratories to assess the THCA initial and confirmatory assays used for federally regulated specimens.

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