Difference between revisions of "Template:Past, Present, and Future of Cannabis Laboratory Testing and Regulation in the United States/Laboratory testing of cannabis/Methods and guidelines/Contaminant testing"

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[[File:LC MS pic.jpg|right|400px]]'''Pesticides''': Gas and liquid chromatography methods are by and large the staple of testing methods for pesticides, which remain "the hardest analyses that are going to be done in the cannabis industry."<ref name="CassidayTheHighs16">{{cite web |url=https://www.aocs.org/stay-informed/inform-magazine/featured-articles/the-highs-and-lows-of-cannabis-testing-october-2016 |title=The Highs and Lows of Cannabis Testing |author=Cassiday, L. |work=INFORM |publisher=American Oil Chemists' Society |date=October 2016 |accessdate=13 January 2021}}</ref> Notably, high-performance liquid chromatography–tandem-mass spectrometry (HPLC-MS/MS) tends to be one of the most thorough methods says Emerald Scientific's CTO Amanda Rigdon. "Ninety-five percent of the pesticides out there can be analyzed by HPLC-MS/MS, although there are some that you would need a GC-MS/MS for," she says.<ref name="CassidayTheHighs16" /> A popular sample extraction method for detecting multiple pesticide residues in cannabis is the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method, which shows "acceptable recoveries and relative standard deviations" for almost all known pesticides<ref name="DePalmaChallenges18">{{cite web |url=https://www.labmanager.com/insights/2018/09/challenges-of-cannabis-contaminant-testing |title=Challenges of Cannabis Contaminant Testing |author=DePalma, A. |work=Lab Manager |publisher=LabX Media Group |date=10 September 2018 |accessdate=08 January 2020}}</ref><ref name="LCGCTrends16">{{cite web |url=http://images2.advanstar.com/PixelMags/lcgc-na/pdf/2016-08-bg.pdf |format=PDF |title=Real-World Chromatography Applications: Current Trends in Cannabis, Environmental, Food, Pharmaceutical, and Biopharmaceutical Analysis |work=LCGC North America 2016-2017 Annual Industry Trends and Directory Issue |author=LCGC |publisher=UBM |pages=584–7 |date=August 2016 |accessdate=15 November 2018}}</ref><ref name="KowalskiEval17">{{cite journal |title=Evaluation of Modified QuEChERS for Pesticide Analysis in Cannabis |journal=LC GC |author=Kowalski, J.; Dahi, J.H.; Rigdon, A. et al. |volume=35 |issue=5 |pages=8–22 |year=2017 |url=http://www.chromatographyonline.com/evaluation-modified-quechers-pesticide-analysis-cannabis}}</ref><ref name="WinklerPesticide18">{{cite web |url=https://www.labcompare.com/10-Featured-Articles/338461-Pesticide-Testing-for-the-Cannabis-Industry-The-Importance-of-LC-MS-MS-for-Obtaining-Accurate-Results-in-a-Complex-Matrix/ |title=Pesticide Testing for the Cannabis Industry: The Importance of LC-MS/MS for Obtaining Accurate Results in a Complex Matrix |author=Winkler, P.C.; Egerton, D.; Butt, C. et al. |work=Labcompare Featured Articles |publisher=CompareNetworks, Inc |date=06 June 2018 |accessdate=15 November 2018}}</ref>, though the release of heat and increase in pH of QuECHERS may degrade particularly sensitive pesticides in the sample.<ref name="JordanAComp18">{{cite journal |title=A Comprehensive Approach to Pesticide Residue Analysis in Cannabis |Journal=Cannabis Science and Technology  |author=Jordan, R.; Asanuma, L.; Miller, D.; Macherone, A. |publisher=UBM |volume=1 |issue=2 |date=19 June 2018 |url=http://www.cannabissciencetech.com/dispersive-solid-phase-extraction-dspe/comprehensive-approach-pesticide-residue-analysis-cannabis}}</ref> However, other methods such as solvent extraction (such as with acetonitrile) with dispersive solid-phase extraction (dSPE) cleanup<ref name="LCGCTrends16" /><ref name="WinklerPesticide18" /><ref name="JordanAComp18" /> and energized dispersive guided extraction (EDGE) may also been used.<ref name="CEMAnal18">{{cite web |url=https://www.azom.com/article.aspx?ArticleID=16383 |title=Analyzing Pesticide Residue of Cannabis |author=CEM Corporation |work=AZO Materials |publisher=AZoNetwork |date=25 July 2018 |accessdate=15 November 2018}}</ref> Common testing methods that have been used, after sample preparation, include<ref name="APHLGuide16">{{cite web |url=https://www.aphl.org/aboutAPHL/publications/Documents/EH-Guide-State-Med-Cannabis-052016.pdf |format=PDF |title=Guidance for State Medical Cannabis Testing Programs |author=Association of Public Health Laboratories |pages=35 |date=May 2016 |accessdate=01 February 2017}}</ref><ref name="ShimadzuCLTS">{{cite web |url=https://www.ssi.shimadzu.com/products/literature/life_science/shimadzu_cannabis_brochure.pdf |archiveurl=https://web.archive.org/web/20160327180816/https://www.ssi.shimadzu.com/products/literature/life_science/shimadzu_cannabis_brochure.pdf |format=PDF |title=Cannabis Testing Laboratory Solutions |publisher=Shimadzu Corporation |archivedate=27 March 2016 |accessdate=21 June 2019}}</ref><ref name="CEMAnal18" /><ref name="KowalskiEval17" /><ref name="WinklerPesticide18" /><ref name="JordanAComp18" />:
[[File:LC MS pic.jpg|right|400px]]'''Pesticides''': Gas and liquid chromatography methods are by and large the staple of testing methods for pesticides, which remain "the hardest analyses that are going to be done in the cannabis industry."<ref name="CassidayTheHighs16">{{cite web |url=https://www.aocs.org/stay-informed/inform-magazine/featured-articles/the-highs-and-lows-of-cannabis-testing-october-2016 |title=The Highs and Lows of Cannabis Testing |author=Cassiday, L. |work=INFORM |publisher=American Oil Chemists' Society |date=October 2016 |accessdate=07 July 2021}}</ref> Notably, high-performance liquid chromatography–tandem-mass spectrometry (HPLC-MS/MS) tends to be one of the most thorough methods says Emerald Scientific's CTO Amanda Rigdon. "Ninety-five percent of the pesticides out there can be analyzed by HPLC-MS/MS, although there are some that you would need a GC-MS/MS for," she says.<ref name="CassidayTheHighs16" /> A popular sample extraction method for detecting multiple pesticide residues in cannabis is the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method, which shows "acceptable recoveries and relative standard deviations" for almost all known pesticides<ref name="DePalmaChallenges18">{{cite web |url=https://www.labmanager.com/insights/challenges-of-cannabis-contaminant-testing-1928 |title=Challenges of Cannabis Contaminant Testing |author=DePalma, A. |work=Lab Manager |publisher=LabX Media Group |date=10 September 2018 |accessdate=07 July 2021}}</ref><ref name="LCGCTrends16">{{cite web |url=http://images2.advanstar.com/PixelMags/lcgc-na/pdf/2016-08-bg.pdf |format=PDF |title=Real-World Chromatography Applications: Current Trends in Cannabis, Environmental, Food, Pharmaceutical, and Biopharmaceutical Analysis |work=LCGC North America 2016-2017 Annual Industry Trends and Directory Issue |author=LCGC |publisher=UBM |pages=584–7 |date=August 2016 |accessdate=07 July 2021}}</ref><ref name="KowalskiEval17">{{cite journal |title=Evaluation of Modified QuEChERS for Pesticide Analysis in Cannabis |journal=LC GC |author=Kowalski, J.; Dahi, J.H.; Rigdon, A. et al. |volume=35 |issue=5 |pages=8–22 |year=2017 |url=https://www.chromatographyonline.com/view/evaluation-modified-quechers-pesticide-analysis-cannabis}}</ref><ref name="WinklerPesticide18">{{cite web |url=https://www.labcompare.com/10-Featured-Articles/338461-Pesticide-Testing-for-the-Cannabis-Industry-The-Importance-of-LC-MS-MS-for-Obtaining-Accurate-Results-in-a-Complex-Matrix/ |title=Pesticide Testing for the Cannabis Industry: The Importance of LC-MS/MS for Obtaining Accurate Results in a Complex Matrix |author=Winkler, P.C.; Egerton, D.; Butt, C. et al. |work=Labcompare Featured Articles |publisher=CompareNetworks, Inc |date=06 June 2018 |accessdate=07 July 2021}}</ref>, though the release of heat and increase in pH of QuECHERS may degrade particularly sensitive pesticides in the sample.<ref name="JordanAComp18">{{cite journal |title=A Comprehensive Approach to Pesticide Residue Analysis in Cannabis |Journal=Cannabis Science and Technology  |author=Jordan, R.; Asanuma, L.; Miller, D.; Macherone, A. |publisher=UBM |volume=1 |issue=2 |date=19 June 2018 |url=https://www.cannabissciencetech.com/view/comprehensive-approach-pesticide-residue-analysis-cannabis}}</ref> However, other methods such as solvent extraction (such as with acetonitrile) with dispersive solid-phase extraction (dSPE) cleanup<ref name="LCGCTrends16" /><ref name="WinklerPesticide18" /><ref name="JordanAComp18" /> and energized dispersive guided extraction (EDGE) may also been used.<ref name="CEMAnal18">{{cite web |url=https://www.azom.com/article.aspx?ArticleID=16383 |title=Analyzing Pesticide Residue of Cannabis |author=CEM Corporation |work=AZO Materials |publisher=AZoNetwork |date=25 July 2018 |accessdate=07 July 2021}}</ref> Common testing methods that have been used, after sample preparation, include<ref name="APHLGuide16">{{cite web |url=https://www.aphl.org/aboutAPHL/publications/Documents/EH-Guide-State-Med-Cannabis-052016.pdf |format=PDF |title=Guidance for State Medical Cannabis Testing Programs |author=Association of Public Health Laboratories |pages=35 |date=May 2016 |accessdate=07 July 2021}}</ref><ref name="ShimadzuCLTS">{{cite web |url=https://www.ssi.shimadzu.com/products/literature/life_science/shimadzu_cannabis_brochure.pdf |archiveurl=https://web.archive.org/web/20160327180816/https://www.ssi.shimadzu.com/products/literature/life_science/shimadzu_cannabis_brochure.pdf |format=PDF |title=Cannabis Testing Laboratory Solutions |publisher=Shimadzu Corporation |archivedate=27 March 2016 |accessdate=07 July 2021}}</ref><ref name="CEMAnal18" /><ref name="KowalskiEval17" /><ref name="WinklerPesticide18" /><ref name="JordanAComp18" />:


* Gas chromatography–electron capture detection (GC-ECD)
* Gas chromatography–electron capture detection (GC-ECD)
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* Liquid chromatography–tandem-mass spectrometry (LC-MS/MS; also high-performance or HPLC-MS/MS)
* Liquid chromatography–tandem-mass spectrometry (LC-MS/MS; also high-performance or HPLC-MS/MS)


For quantification of pesticides in cannabis, the AOAC's SMPR 2018.011, EPA's Residue Analytical Methods (RAM), and FDA's Pesticide Analytical Manual (PAM) provide guidance to labs.<ref name="APHLGuide16" /><ref name="SMPR2018.011">{{cite web |url=https://www.aoac.org/wp-content/uploads/2020/01/SMPR2018_011.pdf |format=PDF |title=AOAC SMPR 2018.011 - Standard Method Performance Requirements (SMPRs) for Identification and Quantitation of Selected Pesticide Residues in Dried Cannabis Materials |author=Association of Official Agricultural Chemists |date=26 August 2018 |accessdate=25 February 2020}}</ref><ref name="EPAResidue17">{{cite web |url=https://archive.epa.gov/pesticides/methods/rammethods/web/html/ram12b.html |title=Residue Analytical Methods (RAM) |publisher=United States Environmental Protection Agency |date=20 February 2016 |accessdate=14 February 2017}}</ref><ref name="FDA_PAM">{{cite web |url=http://www.fda.gov/Food/FoodScienceResearch/LaboratoryMethods/ucm2006955.htm |title=Pesticide Analytical Manual (PAM) |publisher=United States Food and Drug Administration |date=07 June 2015 |accessdate=14 February 2017}}</ref>
For quantification of pesticides in cannabis, the AOAC's SMPR 2018.011, EPA's Residue Analytical Methods (RAM), and FDA's Pesticide Analytical Manual (PAM) provide guidance to labs.<ref name="APHLGuide16" /><ref name="SMPR2018.011">{{cite web |url=https://www.aoac.org/wp-content/uploads/2020/01/SMPR2018_011.pdf |format=PDF |title=AOAC SMPR 2018.011 - Standard Method Performance Requirements (SMPRs) for Identification and Quantitation of Selected Pesticide Residues in Dried Cannabis Materials |author=Association of Official Agricultural Chemists |date=26 August 2018 |accessdate=07 July 2021}}</ref><ref name="EPAResidue17">{{cite web |url=https://archive.epa.gov/pesticides/methods/rammethods/web/html/ram12b.html |title=Residue Analytical Methods (RAM) |publisher=United States Environmental Protection Agency |date=20 February 2016 |accessdate=07 July 2021}}</ref><ref name="FDA_PAM">{{cite web |url=https://www.fda.gov/food/laboratory-methods-food/pesticide-analytical-manual-pam |title=Pesticide Analytical Manual (PAM) |publisher=United States Food and Drug Administration |date=19 September 2018 |accessdate=07 July 2021}}</ref>




'''Solvents''': Testing for solvents is largely standardized into a few options, which have parallels to existing pharmaceutical testing standards outlined in Chapter 467 of ''United States Pharmacopeia and The National Formulary'' (USP <467>)<ref name="USPNF467">{{cite web |url=https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |archiveurl=https://web.archive.org/web/20160804174451/https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |format=PDF |title=<467> Residual Solvents |work=United States Pharmacopeia and The National Formulary |publisher=United States Pharmacopeial Convention |date=01 July 2007 |archivedate=04 August 2016 |accessdate=21 June 2019}}</ref><ref name="APHLGuide16" /><ref name="CassidayTheHighs16" /><ref name="ShimadzuCLTS" /><ref name="PocevaOpti16">{{cite journal |title=Optimization of HS-GC-FID-MS Method for Residual Solvent Profiling in Active Pharmaceutical Ingredients Using DoE |journal=Journal of Chromatographic Science |author=Poceva Panovska, A.; Acevska, J.; Stefkov, G. et al. |volume=54 |issue=2 |pages=103–11 |year=2016 |doi=10.1093/chromsci/bmv123 |pmid=26290585}}</ref><ref name="L'HeureuxAdvancing18">{{cite web |url=http://www.cannabissciencetech.com/cannabis-voices/advancing-chromatography-methods-cannabis-analysis |title=Advancing Chromatography Methods for Cannabis Analysis |work=Cannabis Science and Technology |author=L'Heureux, M.L. |publisher=UBM |date=20 April 2018 |accessdate=21 June 2019}}</ref>:
'''Solvents''': Testing for solvents is largely standardized into a few options, which have parallels to existing pharmaceutical testing standards outlined in Chapter 467 of ''United States Pharmacopeia and The National Formulary'' (USP <467>)<ref name="USPNF467">{{cite web |url=https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |archiveurl=https://web.archive.org/web/20160804174451/https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |format=PDF |title=<467> Residual Solvents |work=United States Pharmacopeia and The National Formulary |publisher=United States Pharmacopeial Convention |date=01 July 2007 |archivedate=04 August 2016 |accessdate=07 July 2021}}</ref><ref name="APHLGuide16" /><ref name="CassidayTheHighs16" /><ref name="ShimadzuCLTS" /><ref name="PocevaOpti16">{{cite journal |title=Optimization of HS-GC-FID-MS Method for Residual Solvent Profiling in Active Pharmaceutical Ingredients Using DoE |journal=Journal of Chromatographic Science |author=Poceva Panovska, A.; Acevska, J.; Stefkov, G. et al. |volume=54 |issue=2 |pages=103–11 |year=2016 |doi=10.1093/chromsci/bmv123 |pmid=26290585}}</ref><ref name="L'HeureuxAdvancing18">{{cite web |url=https://www.cannabissciencetech.com/view/advancing-chromatography-methods-cannabis-analysis |title=Advancing Chromatography Methods for Cannabis Analysis |work=Cannabis Science and Technology |author=L'Heureux, M.L. |publisher=UBM |date=20 April 2018 |accessdate=07 July 2021}}</ref>:


* Headspace–gas chromatography/mass spectrometry (HS-GC/MS)
* Headspace–gas chromatography/mass spectrometry (HS-GC/MS)
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* Full evaporation technique–headspace–gas chromatography–flame ionization detection (FET-HS-GC-FID)
* Full evaporation technique–headspace–gas chromatography–flame ionization detection (FET-HS-GC-FID)


Massachusetts and Oregon—and likely other states—have used a variety of guidance documents such as USP <467>, reports from the Commission of the European Communities' Scientific Committee on Food (now the European Food Safety Authority), and the International Conference on Harmonization's (ICH) Q3C(R5)<ref name="APHLGuide16" /><ref name="MDPHResponse">{{cite web |url=http://www.mass.gov/eohhs/docs/dph/quality/medical-marijuana/lab-protocols/external-comment-response-020416-final.pdf |format=PDF |title=Response to Public Comments |author=Bureau of Healthcare Safety and Quality |publisher=Massachusetts Department of Public Health |date=12 February 2016 |accessdate=14 February 2017}}</ref><ref name="FarrerTech15">{{cite web |url=https://public.health.oregon.gov/PreventionWellness/marijuana/Documents/oha-8964-technical-report-marijuana-contaminant-testing.pdf |format=PDF |title=Technical Report: Oregon Health Authority’s Process to Determine Which Types of Contaminants to Test for in Cannabis Products, and Levels for Action |author=Farrer, D.G. |publisher=Oregon Health Authority |date=December 2015 |accessdate=09 February 2017}}</ref><ref name="USPNF467">{{cite web |url=https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |archiveurl=https://web.archive.org/web/20160804174451/https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |format=PDF |title=<467> Residual Solvents |work=United States Pharmacopeia and The National Formulary |publisher=United States Pharmacopeial Convention |date=01 July 2007 |archivedate=04 August 2016 |accessdate=21 June 2019}}</ref> to set their action level testing values for particular solvents. The AOAC provides another standardized option in the form of their SMPR 2019.002.<ref name="SMPR2019.002">{{cite web |url=https://www.aoac.org/wp-content/uploads/2019/10/SMPR-2019_002.pdf |format=PDF |title=AOAC SMPR 2019.002 - Standard Method Performance Requirements (SMPRs) for Identification and Quantitation of Selected Residual Solvents in Cannabis-Derived Materials |author=Association of Official Agricultural Chemists |date=09 October 2019 |accessdate=25 February 2020}}</ref>
Massachusetts and Oregon—and likely other states—have used a variety of guidance documents such as USP <467>, reports from the Commission of the European Communities' Scientific Committee on Food (now the European Food Safety Authority), and the International Conference on Harmonization's (ICH) Q3C(R5)<ref name="APHLGuide16" /><ref name="MDPHResponse">{{cite web |url=http://www.mass.gov/eohhs/docs/dph/quality/medical-marijuana/lab-protocols/external-comment-response-020416-final.pdf |archiveurl=https://web.archive.org/web/20171013214634/https://www.mass.gov/eohhs/docs/dph/quality/medical-marijuana/lab-protocols/external-comment-response-020416-final.pdf |format=PDF |title=Response to Public Comments |author=Bureau of Healthcare Safety and Quality |publisher=Massachusetts Department of Public Health |date=12 February 2016 |archivedate=13 October 2017 |accessdate=07 July 2021}}</ref><ref name="FarrerTech15">{{cite web |url=https://www.oregon.gov/oha/ph/PreventionWellness/marijuana/Documents/oha-8964-technical-report-marijuana-contaminant-testing.pdf |format=PDF |title=Technical Report: Oregon Health Authority’s Process to Determine Which Types of Contaminants to Test for in Cannabis Products, and Levels for Action |author=Farrer, D.G. |publisher=Oregon Health Authority |date=December 2015 |accessdate=07 July 2021}}</ref><ref name="USPNF467">{{cite web |url=https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |archiveurl=https://web.archive.org/web/20160804174451/https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf |format=PDF |title=<467> Residual Solvents |work=United States Pharmacopeia and The National Formulary |publisher=United States Pharmacopeial Convention |date=01 July 2007 |archivedate=04 August 2016 |accessdate=07 July 2021}}</ref> to set their action level testing values for particular solvents. The AOAC provides another standardized option in the form of their SMPR 2019.002.<ref name="SMPR2019.002">{{cite web |url=https://www.aoac.org/wp-content/uploads/2019/10/SMPR-2019_002.pdf |format=PDF |title=AOAC SMPR 2019.002 - Standard Method Performance Requirements (SMPRs) for Identification and Quantitation of Selected Residual Solvents in Cannabis-Derived Materials |author=Association of Official Agricultural Chemists |date=09 October 2019 |accessdate=07 July 2021}}</ref>




'''Heavy metals''': The methods used for quantifying levels of highly toxic metals in plants depend on ease-of-use, level of accuracy, and overall cost. Sample preparation typically includes the use of closed-vessel [[microwave digestion]] to get the sample into solution for analysis.<ref name="CEMAnal18" /><ref name="BoyleSelecting18">{{cite journal |title=Selecting Microwave Digestion Technology for Measuring Heavy Metals in Cannabis Products |journal=Cannabis Science and Technology |author=Boyle, R.; Ferrell, E. |volume=1 |issue=3 |date=21 September 2018 |url=http://www.cannabissciencetech.com/metals/selecting-microwave-digestion-technology-measuring-heavy-metals-cannabis-products}}</ref> Once prepared, the following methods are most common for testing cannabis and other plants for heavy metals<ref name="KuzdzalACloser16">{{cite web |url=https://www.ssi.shimadzu.com/sites/ssi.shimadzu.com/files/Industry/Literature/Shimadzu_Whitepaper_Emerging_Cannabis_Industry.pdf |format=PDF |title=A Closer Look at Cannabis Testing |author=Kuzdzal, S.; Clifford, R.; Winkler, P.; Bankert, W. |publisher=Shimadzu Corporation |date=December 2017 |accessdate=13 January 2021}}</ref><ref name="APHLGuide16" /><ref name="CassidayTheHighs16" /><ref name="DavisAnalysis15">{{cite web |url=http://www.ssi.shimadzu.com/products/literature/aas/ssi-icp-002.pdf |format=PDF |title=Analysis of "The Big Four" Heavy Metals in Cannabis by USN-ICP-OES |author=Davis, D.; Long, K.; Masone, J.; Firmin, P. |publisher=Shimadzu Corporation |date=August 2015 |accessdate=14 February 2017}}</ref><ref name="ShimadzuCLTS" />:
'''Heavy metals''': The methods used for quantifying levels of highly toxic metals in plants depend on ease-of-use, level of accuracy, and overall cost. Sample preparation typically includes the use of closed-vessel [[microwave digestion]] to get the sample into solution for analysis.<ref name="CEMAnal18" /><ref name="BoyleSelecting18">{{cite journal |title=Selecting Microwave Digestion Technology for Measuring Heavy Metals in Cannabis Products |journal=Cannabis Science and Technology |author=Boyle, R.; Ferrell, E. |volume=1 |issue=3 |date=21 September 2018 |url=https://www.cannabissciencetech.com/view/selecting-microwave-digestion-technology-measuring-heavy-metals-cannabis-products}}</ref> Once prepared, the following methods are most common for testing cannabis and other plants for heavy metals<ref name="KuzdzalACloser16">{{cite web |url=https://www.ssi.shimadzu.com/sites/ssi.shimadzu.com/files/Industry/Literature/Shimadzu_Whitepaper_Emerging_Cannabis_Industry.pdf |format=PDF |title=A Closer Look at Cannabis Testing |author=Kuzdzal, S.; Clifford, R.; Winkler, P.; Bankert, W. |publisher=Shimadzu Corporation |date=December 2017 |accessdate=07 July 2021}}</ref><ref name="APHLGuide16" /><ref name="CassidayTheHighs16" /><ref name="DavisAnalysis15">{{cite web |url=http://www.ssi.shimadzu.com/products/literature/aas/ssi-icp-002.pdf |archiveurl=https://web.archive.org/web/20170214222831/http://www.ssi.shimadzu.com/products/literature/aas/ssi-icp-002.pdf |format=PDF |title=Analysis of "The Big Four" Heavy Metals in Cannabis by USN-ICP-OES |author=Davis, D.; Long, K.; Masone, J.; Firmin, P. |publisher=Shimadzu Corporation |date=August 2015 |archivedate=14 February 2017 |accessdate=07 July 2021}}</ref><ref name="ShimadzuCLTS" />:


* [[Inductively coupled plasma atomic emission spectroscopy|Inductively coupled plasma–atomic emission spectroscopy]] (ICP-AES), sometimes called inductively coupled plasma optical emission spectrometry (ICP-OES) (at times coupled with an ultrasonic nebulizer)
* [[Inductively coupled plasma atomic emission spectroscopy|Inductively coupled plasma–atomic emission spectroscopy]] (ICP-AES), sometimes called inductively coupled plasma optical emission spectrometry (ICP-OES) (at times coupled with an ultrasonic nebulizer)
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* Inductively coupled plasma–tandem-mass spectroscopy (ICP-MS/MS)
* Inductively coupled plasma–tandem-mass spectroscopy (ICP-MS/MS)


For quantification of metals in cannabis, the U.S. FDA's ICP-MS methodology document is often used.<ref name="APHLGuide16" /><ref name="FDAAnalysisofFoods11">{{cite web |url=http://www.fda.gov/downloads/Food/FoodborneIllnessContaminants/Metals/UCM272693.pdf |format=PDF |title=Analysis of Foods for As, Cd, Cr, Hg and Pb by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) |publisher=United States Food and Drug Administration, Center for Food Safety and Applied Nutrition |date=25 April 2011 |accessdate=14 February 2017}}</ref>
For quantification of metals in cannabis, the U.S. FDA's ICP-MS methodology document is often used.<ref name="APHLGuide16" /><ref name="FDAAnalysisofFoods11">{{cite web |url=http://www.fda.gov/downloads/Food/FoodborneIllnessContaminants/Metals/UCM272693.pdf |archiveurl=https://web.archive.org/web/20170218071933/http://www.fda.gov/downloads/Food/FoodborneIllnessContaminants/Metals/UCM272693.pdf |format=PDF |title=Analysis of Foods for As, Cd, Cr, Hg and Pb by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) |publisher=United States Food and Drug Administration, Center for Food Safety and Applied Nutrition |date=25 April 2011 |archivedate=18 February 2017 |accessdate=07 July 2021}}</ref>




'''Mycotoxins and microorganisms''': A standard method of testing for the existence of microorganisms is through the process of culturing a sample in a Petri dish, a common diagnostic method in microbiology. [[ELISA|Enzyme-linked immunosorbent assay]] (ELISA) is also used, particularly to identify mycotoxins. However, Petri culture analysis isn't rigorous, and ELISA can be time consuming, as it's limited to one mycotoxin per test.<ref name="KuzdzalACloser16" /><ref name="CassidayTheHighs16" /><ref name="KennardYouAre16">{{cite web |url=https://populace.tantaluslabs.com/you-are-probably-smoking-mouldy-weed-why-does-quality-assurance-matter/ |title=You are Probably Smoking Mouldy Weed - Why Does Quality Assurance Matter? |work=Populace |author=Kennard, M. |publisher=Tantalus Labs |date=02 June 2014 |accessdate=21 June 2019}}</ref> The following are other, more precise techniques that are improving laboratorians' analyses, particularly using DNA snippets of microbiological contaminants<ref name="KuzdzalACloser16" /><ref name="CassidayTheHighs16" /><ref name="KennardYouAre16" /><ref name="ThompsonAMicro16">{{cite journal |title=A microbiome assessment of medical marijuana |journal=Clinical Microbiology and Infection |author=Thompson III, G.R.; Tuscano, J.M.; Dennis, M. et al. |pages=S1198-743X(16)30605-X |year=2017 |doi=10.1016/j.cmi.2016.12.001 |pmid=27956269}}</ref><ref name="L'HeureuxTesting18">{{cite web |url=http://www.cannabissciencetech.com/cannabis-voices/testing-pesticides-and-mycotoxins-cannabis-how-meet-regulatory-requirements |title=Testing for Pesticides and Mycotoxins in Cannabis: How to Meet Regulatory Requirements |work=Cannabis Science and Technology |author=L'Heureux, M.L. |publisher=UBM |date=06 August 2018 |accessdate=21 June 2019}}</ref>:
'''Mycotoxins and microorganisms''': A standard method of testing for the existence of microorganisms is through the process of culturing a sample in a Petri dish, a common diagnostic method in microbiology. [[ELISA|Enzyme-linked immunosorbent assay]] (ELISA) is also used, particularly to identify mycotoxins. However, Petri culture analysis isn't rigorous, and ELISA can be time consuming, as it's limited to one mycotoxin per test.<ref name="KuzdzalACloser16" /><ref name="CassidayTheHighs16" /><ref name="KennardYouAre16">{{cite web |url=https://populace.tantaluslabs.com/you-are-probably-smoking-mouldy-weed-why-does-quality-assurance-matter/ |title=You are Probably Smoking Mouldy Weed - Why Does Quality Assurance Matter? |work=Populace |author=Kennard, M. |publisher=Tantalus Labs |date=02 June 2014 |accessdate=07 July 2021}}</ref> The following are other, more precise techniques that are improving laboratorians' analyses, particularly using DNA snippets of microbiological contaminants<ref name="KuzdzalACloser16" /><ref name="CassidayTheHighs16" /><ref name="KennardYouAre16" /><ref name="ThompsonAMicro16">{{cite journal |title=A microbiome assessment of medical marijuana |journal=Clinical Microbiology and Infection |author=Thompson III, G.R.; Tuscano, J.M.; Dennis, M. et al. |pages=S1198-743X(16)30605-X |year=2017 |doi=10.1016/j.cmi.2016.12.001 |pmid=27956269}}</ref><ref name="L'HeureuxTesting18">{{cite web |url=https://www.cannabissciencetech.com/view/testing-pesticides-and-mycotoxins-cannabis-how-meet-regulatory-requirements |title=Testing for Pesticides and Mycotoxins in Cannabis: How to Meet Regulatory Requirements |work=Cannabis Science and Technology |author=L'Heureux, M.L. |publisher=UBM |date=06 August 2018 |accessdate=07 July 2021}}</ref>:


* [[Real-time polymerase chain reaction|Quantitative polymerase chain reaction]] (qPCR)
* [[Real-time polymerase chain reaction|Quantitative polymerase chain reaction]] (qPCR)
Line 38: Line 38:
* Liquid chromatography–atmospheric pressure chemical ionization–tandem-mass spectrometry (LC-APCI-MS/MS)
* Liquid chromatography–atmospheric pressure chemical ionization–tandem-mass spectrometry (LC-APCI-MS/MS)


The extent of mycotoxin testing required remains in question by several entities. The APHL claims "[t]here is no readily available evidence to support the contention that cannabis harbors significant levels of mycotoxins."<ref name="APHLGuide16" /> The Oregon Health Authority takes a more middle-ground approach, noting that testing for ''E. coli'' and ''Salmonella'' will "protect public health," though ''Aspergillus'' only deserves a warning for people with suppressed immune systems due to its prevalence in the environment.<ref name="FarrerTech15" /> USP <561> recommendations largely limit mycotoxin testing of botanical products to those borne from root or [[rhizome]] material<ref name="USPNF561">{{cite web |url=https://hmc.usp.org/sites/default/files/documents/HMC/GCs-Pdfs/c561.pdf |format=PDF |title=<561> Articles of Botanical Origin |work=United States Pharmacopeia and The National Formulary |publisher=United States Pharmacopeial Convention |date=01 July 2007 |accessdate=15 February 2017}}</ref>, "which THC-containing cannabis products presumably do not possess," emphasizes the APHL.<ref name="APHLGuide16" /> Regardless, U.S. Pharmacopeia's Chapter 561 remains a useful document for testing guidelines and limits regarding microbials<ref name="USPNF561" /><ref name="APHLGuide16" />, as does the AOAC's SMPR 2019.001 for the detection of ''Aspergillus''.<ref name="SMPR2019.001">{{cite web |url=https://www.aoac.org/wp-content/uploads/2019/10/SMPR-2019_001.pdf |format=PDF |title=AOAC SMPR 2019.001 - Standard Method Performance Requirements (SMPRs) for Detection of ''Aspergillus'' in Cannabis and Cannabis Products |author=Association of Official Agricultural Chemists |date=09 October 2019 |accessdate=25 February 2020}}</ref> In the less common case of dealing with powdered cannabis—a relatively new THC extract form—Chapter 2023 provides at least some testing parallels, though Dr. Tony Cundell, a microbiologist consulting for the pharmaceutical industry, suggests USP <2023> doesn't go far enough for immunocompromised patients.<ref name="CundellMicro15">{{cite web |url=http://www.americanpharmaceuticalreview.com/Featured-Articles/177487-Microbiological-Attributes-of-Powdered-Cannabis/ |title=Microbiological attributes of powdered cannabis |work=American Pharmaceutical Review |author=Cundell, T. |publisher=CompareNetworks, Inc |date=31 July 2015 |accessdate=15 February 2017}}</ref>
The extent of mycotoxin testing required remains in question by several entities. The APHL claims "[t]here is no readily available evidence to support the contention that cannabis harbors significant levels of mycotoxins."<ref name="APHLGuide16" /> The Oregon Health Authority takes a more middle-ground approach, noting that testing for ''E. coli'' and ''Salmonella'' will "protect public health," though ''Aspergillus'' only deserves a warning for people with suppressed immune systems due to its prevalence in the environment.<ref name="FarrerTech15" /> USP <561> recommendations largely limit mycotoxin testing of botanical products to those borne from root or [[rhizome]] material<ref name="USPNF561">{{cite web |url=https://hmc.usp.org/sites/default/files/documents/HMC/GCs-Pdfs/c561.pdf |archiveurl=https://web.archive.org/web/20171202221121/https://hmc.usp.org/sites/default/files/documents/HMC/GCs-Pdfs/c561.pdf |format=PDF |title=<561> Articles of Botanical Origin |work=United States Pharmacopeia and The National Formulary |publisher=United States Pharmacopeial Convention |date=01 July 2007 |archivedate=02 December 2017 |accessdate=07 July 2021}}</ref>, "which THC-containing cannabis products presumably do not possess," emphasizes the APHL.<ref name="APHLGuide16" /> Regardless, U.S. Pharmacopeia's Chapter 561 remains a useful document for testing guidelines and limits regarding microbials<ref name="USPNF561" /><ref name="APHLGuide16" />, as does the AOAC's SMPR 2019.001 for the detection of ''Aspergillus''.<ref name="SMPR2019.001">{{cite web |url=https://www.aoac.org/wp-content/uploads/2019/10/SMPR-2019_001.pdf |format=PDF |title=AOAC SMPR 2019.001 - Standard Method Performance Requirements (SMPRs) for Detection of ''Aspergillus'' in Cannabis and Cannabis Products |author=Association of Official Agricultural Chemists |date=09 October 2019 |accessdate=07 July 2021}}</ref> In the less common case of dealing with powdered cannabis—a relatively new THC extract form—Chapter 2023 provides at least some testing parallels, though Dr. Tony Cundell, a microbiologist consulting for the pharmaceutical industry, suggests USP <2023> doesn't go far enough for immunocompromised patients.<ref name="CundellMicro15">{{cite web |url=https://www.americanpharmaceuticalreview.com/Featured-Articles/177487-Microbiological-Attributes-of-Powdered-Cannabis/ |title=Microbiological attributes of powdered cannabis |work=American Pharmaceutical Review |author=Cundell, T. |publisher=CompareNetworks, Inc |date=31 July 2015 |accessdate=07 July 2021}}</ref>


Somewhat related and worth mentioning is moisture content testing. As previously mentioned, warm, moist environments are conducive to microorganism growth, and regularly measuring water activity is useful for the prevention of microbial growth.<ref name="FarrerTech15" /> The APHL references specifications from the Dutch Office of Medical Cannabis that recommend water content be between five to ten percent in cannabis.<ref name="APHLGuide16" />
Somewhat related and worth mentioning is moisture content testing. As previously mentioned, warm, moist environments are conducive to microorganism growth, and regularly measuring water activity is useful for the prevention of microbial growth.<ref name="FarrerTech15" /> The APHL references specifications from the Dutch Office of Medical Cannabis that recommend water content be between five to ten percent in cannabis.<ref name="APHLGuide16" />

Revision as of 19:20, 7 July 2021

LC MS pic.jpg

Pesticides: Gas and liquid chromatography methods are by and large the staple of testing methods for pesticides, which remain "the hardest analyses that are going to be done in the cannabis industry."[1] Notably, high-performance liquid chromatography–tandem-mass spectrometry (HPLC-MS/MS) tends to be one of the most thorough methods says Emerald Scientific's CTO Amanda Rigdon. "Ninety-five percent of the pesticides out there can be analyzed by HPLC-MS/MS, although there are some that you would need a GC-MS/MS for," she says.[1] A popular sample extraction method for detecting multiple pesticide residues in cannabis is the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method, which shows "acceptable recoveries and relative standard deviations" for almost all known pesticides[2][3][4][5], though the release of heat and increase in pH of QuECHERS may degrade particularly sensitive pesticides in the sample.[6] However, other methods such as solvent extraction (such as with acetonitrile) with dispersive solid-phase extraction (dSPE) cleanup[3][5][6] and energized dispersive guided extraction (EDGE) may also been used.[7] Common testing methods that have been used, after sample preparation, include[8][9][7][4][5][6]:

  • Gas chromatography–electron capture detection (GC-ECD)
  • Gas chromatography–mass spectrometry (GC-MS)
  • Gas chromatography–tandem-mass spectrometry (GC-MS/MS)
  • Liquid chromatography–mass spectrometry (LC-MS; also high-performance or HPLC-MS)
  • Liquid chromatography–tandem-mass spectrometry (LC-MS/MS; also high-performance or HPLC-MS/MS)

For quantification of pesticides in cannabis, the AOAC's SMPR 2018.011, EPA's Residue Analytical Methods (RAM), and FDA's Pesticide Analytical Manual (PAM) provide guidance to labs.[8][10][11][12]


Solvents: Testing for solvents is largely standardized into a few options, which have parallels to existing pharmaceutical testing standards outlined in Chapter 467 of United States Pharmacopeia and The National Formulary (USP <467>)[13][8][1][9][14][15]:

  • Headspace–gas chromatography/mass spectrometry (HS-GC/MS)
  • Headspace–gas chromatography–flame ionization detection–mass spectrometry (HS-GC-FID-MS)
  • Full evaporation technique–headspace–gas chromatography–flame ionization detection (FET-HS-GC-FID)

Massachusetts and Oregon—and likely other states—have used a variety of guidance documents such as USP <467>, reports from the Commission of the European Communities' Scientific Committee on Food (now the European Food Safety Authority), and the International Conference on Harmonization's (ICH) Q3C(R5)[8][16][17][13] to set their action level testing values for particular solvents. The AOAC provides another standardized option in the form of their SMPR 2019.002.[18]


Heavy metals: The methods used for quantifying levels of highly toxic metals in plants depend on ease-of-use, level of accuracy, and overall cost. Sample preparation typically includes the use of closed-vessel microwave digestion to get the sample into solution for analysis.[7][19] Once prepared, the following methods are most common for testing cannabis and other plants for heavy metals[20][8][1][21][9]:

For quantification of metals in cannabis, the U.S. FDA's ICP-MS methodology document is often used.[8][22]


Mycotoxins and microorganisms: A standard method of testing for the existence of microorganisms is through the process of culturing a sample in a Petri dish, a common diagnostic method in microbiology. Enzyme-linked immunosorbent assay (ELISA) is also used, particularly to identify mycotoxins. However, Petri culture analysis isn't rigorous, and ELISA can be time consuming, as it's limited to one mycotoxin per test.[20][1][23] The following are other, more precise techniques that are improving laboratorians' analyses, particularly using DNA snippets of microbiological contaminants[20][1][23][24][25]:

The extent of mycotoxin testing required remains in question by several entities. The APHL claims "[t]here is no readily available evidence to support the contention that cannabis harbors significant levels of mycotoxins."[8] The Oregon Health Authority takes a more middle-ground approach, noting that testing for E. coli and Salmonella will "protect public health," though Aspergillus only deserves a warning for people with suppressed immune systems due to its prevalence in the environment.[17] USP <561> recommendations largely limit mycotoxin testing of botanical products to those borne from root or rhizome material[26], "which THC-containing cannabis products presumably do not possess," emphasizes the APHL.[8] Regardless, U.S. Pharmacopeia's Chapter 561 remains a useful document for testing guidelines and limits regarding microbials[26][8], as does the AOAC's SMPR 2019.001 for the detection of Aspergillus.[27] In the less common case of dealing with powdered cannabis—a relatively new THC extract form—Chapter 2023 provides at least some testing parallels, though Dr. Tony Cundell, a microbiologist consulting for the pharmaceutical industry, suggests USP <2023> doesn't go far enough for immunocompromised patients.[28]

Somewhat related and worth mentioning is moisture content testing. As previously mentioned, warm, moist environments are conducive to microorganism growth, and regularly measuring water activity is useful for the prevention of microbial growth.[17] The APHL references specifications from the Dutch Office of Medical Cannabis that recommend water content be between five to ten percent in cannabis.[8]

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Cassiday, L. (October 2016). "The Highs and Lows of Cannabis Testing". INFORM. American Oil Chemists' Society. https://www.aocs.org/stay-informed/inform-magazine/featured-articles/the-highs-and-lows-of-cannabis-testing-october-2016. Retrieved 07 July 2021. 
  2. ↑ DePalma, A. (10 September 2018). "Challenges of Cannabis Contaminant Testing". Lab Manager. LabX Media Group. https://www.labmanager.com/insights/challenges-of-cannabis-contaminant-testing-1928. Retrieved 07 July 2021. 
  3. ↑ 3.0 3.1 LCGC (August 2016). "Real-World Chromatography Applications: Current Trends in Cannabis, Environmental, Food, Pharmaceutical, and Biopharmaceutical Analysis" (PDF). LCGC North America 2016-2017 Annual Industry Trends and Directory Issue. UBM. pp. 584–7. http://images2.advanstar.com/PixelMags/lcgc-na/pdf/2016-08-bg.pdf. Retrieved 07 July 2021. 
  4. ↑ 4.0 4.1 Kowalski, J.; Dahi, J.H.; Rigdon, A. et al. (2017). "Evaluation of Modified QuEChERS for Pesticide Analysis in Cannabis". LC GC 35 (5): 8–22. https://www.chromatographyonline.com/view/evaluation-modified-quechers-pesticide-analysis-cannabis. 
  5. ↑ 5.0 5.1 5.2 Winkler, P.C.; Egerton, D.; Butt, C. et al. (6 June 2018). "Pesticide Testing for the Cannabis Industry: The Importance of LC-MS/MS for Obtaining Accurate Results in a Complex Matrix". Labcompare Featured Articles. CompareNetworks, Inc. https://www.labcompare.com/10-Featured-Articles/338461-Pesticide-Testing-for-the-Cannabis-Industry-The-Importance-of-LC-MS-MS-for-Obtaining-Accurate-Results-in-a-Complex-Matrix/. Retrieved 07 July 2021. 
  6. ↑ 6.0 6.1 6.2 Jordan, R.; Asanuma, L.; Miller, D.; Macherone, A. (19 June 2018). A Comprehensive Approach to Pesticide Residue Analysis in Cannabis. 1. UBM. https://www.cannabissciencetech.com/view/comprehensive-approach-pesticide-residue-analysis-cannabis. 
  7. ↑ 7.0 7.1 7.2 CEM Corporation (25 July 2018). "Analyzing Pesticide Residue of Cannabis". AZO Materials. AZoNetwork. https://www.azom.com/article.aspx?ArticleID=16383. Retrieved 07 July 2021. 
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 Association of Public Health Laboratories (May 2016). "Guidance for State Medical Cannabis Testing Programs" (PDF). pp. 35. https://www.aphl.org/aboutAPHL/publications/Documents/EH-Guide-State-Med-Cannabis-052016.pdf. Retrieved 07 July 2021. 
  9. ↑ 9.0 9.1 9.2 "Cannabis Testing Laboratory Solutions" (PDF). Shimadzu Corporation. Archived from the original on 27 March 2016. https://web.archive.org/web/20160327180816/https://www.ssi.shimadzu.com/products/literature/life_science/shimadzu_cannabis_brochure.pdf. Retrieved 07 July 2021. 
  10. ↑ Association of Official Agricultural Chemists (26 August 2018). "AOAC SMPR 2018.011 - Standard Method Performance Requirements (SMPRs) for Identification and Quantitation of Selected Pesticide Residues in Dried Cannabis Materials" (PDF). https://www.aoac.org/wp-content/uploads/2020/01/SMPR2018_011.pdf. Retrieved 07 July 2021. 
  11. ↑ "Residue Analytical Methods (RAM)". United States Environmental Protection Agency. 20 February 2016. https://archive.epa.gov/pesticides/methods/rammethods/web/html/ram12b.html. Retrieved 07 July 2021. 
  12. ↑ "Pesticide Analytical Manual (PAM)". United States Food and Drug Administration. 19 September 2018. https://www.fda.gov/food/laboratory-methods-food/pesticide-analytical-manual-pam. Retrieved 07 July 2021. 
  13. ↑ 13.0 13.1 "<467> Residual Solvents" (PDF). United States Pharmacopeia and The National Formulary. United States Pharmacopeial Convention. 1 July 2007. Archived from the original on 04 August 2016. https://web.archive.org/web/20160804174451/https://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter467Current.pdf. Retrieved 07 July 2021. 
  14. ↑ Poceva Panovska, A.; Acevska, J.; Stefkov, G. et al. (2016). "Optimization of HS-GC-FID-MS Method for Residual Solvent Profiling in Active Pharmaceutical Ingredients Using DoE". Journal of Chromatographic Science 54 (2): 103–11. doi:10.1093/chromsci/bmv123. PMID 26290585. 
  15. ↑ L'Heureux, M.L. (20 April 2018). "Advancing Chromatography Methods for Cannabis Analysis". Cannabis Science and Technology. UBM. https://www.cannabissciencetech.com/view/advancing-chromatography-methods-cannabis-analysis. Retrieved 07 July 2021. 
  16. ↑ Bureau of Healthcare Safety and Quality (12 February 2016). "Response to Public Comments" (PDF). Massachusetts Department of Public Health. Archived from the original on 13 October 2017. https://web.archive.org/web/20171013214634/https://www.mass.gov/eohhs/docs/dph/quality/medical-marijuana/lab-protocols/external-comment-response-020416-final.pdf. Retrieved 07 July 2021. 
  17. ↑ 17.0 17.1 17.2 Farrer, D.G. (December 2015). "Technical Report: Oregon Health Authority’s Process to Determine Which Types of Contaminants to Test for in Cannabis Products, and Levels for Action" (PDF). Oregon Health Authority. https://www.oregon.gov/oha/ph/PreventionWellness/marijuana/Documents/oha-8964-technical-report-marijuana-contaminant-testing.pdf. Retrieved 07 July 2021. 
  18. ↑ Association of Official Agricultural Chemists (9 October 2019). "AOAC SMPR 2019.002 - Standard Method Performance Requirements (SMPRs) for Identification and Quantitation of Selected Residual Solvents in Cannabis-Derived Materials" (PDF). https://www.aoac.org/wp-content/uploads/2019/10/SMPR-2019_002.pdf. Retrieved 07 July 2021. 
  19. ↑ Boyle, R.; Ferrell, E. (21 September 2018). "Selecting Microwave Digestion Technology for Measuring Heavy Metals in Cannabis Products". Cannabis Science and Technology 1 (3). https://www.cannabissciencetech.com/view/selecting-microwave-digestion-technology-measuring-heavy-metals-cannabis-products. 
  20. ↑ 20.0 20.1 20.2 Kuzdzal, S.; Clifford, R.; Winkler, P.; Bankert, W. (December 2017). "A Closer Look at Cannabis Testing" (PDF). Shimadzu Corporation. https://www.ssi.shimadzu.com/sites/ssi.shimadzu.com/files/Industry/Literature/Shimadzu_Whitepaper_Emerging_Cannabis_Industry.pdf. Retrieved 07 July 2021. 
  21. ↑ Davis, D.; Long, K.; Masone, J.; Firmin, P. (August 2015). "Analysis of "The Big Four" Heavy Metals in Cannabis by USN-ICP-OES" (PDF). Shimadzu Corporation. Archived from the original on 14 February 2017. https://web.archive.org/web/20170214222831/http://www.ssi.shimadzu.com/products/literature/aas/ssi-icp-002.pdf. Retrieved 07 July 2021. 
  22. ↑ "Analysis of Foods for As, Cd, Cr, Hg and Pb by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS)" (PDF). United States Food and Drug Administration, Center for Food Safety and Applied Nutrition. 25 April 2011. Archived from the original on 18 February 2017. https://web.archive.org/web/20170218071933/http://www.fda.gov/downloads/Food/FoodborneIllnessContaminants/Metals/UCM272693.pdf. Retrieved 07 July 2021. 
  23. ↑ 23.0 23.1 Kennard, M. (2 June 2014). "You are Probably Smoking Mouldy Weed - Why Does Quality Assurance Matter?". Populace. Tantalus Labs. https://populace.tantaluslabs.com/you-are-probably-smoking-mouldy-weed-why-does-quality-assurance-matter/. Retrieved 07 July 2021. 
  24. ↑ Thompson III, G.R.; Tuscano, J.M.; Dennis, M. et al. (2017). "A microbiome assessment of medical marijuana". Clinical Microbiology and Infection: S1198-743X(16)30605-X. doi:10.1016/j.cmi.2016.12.001. PMID 27956269. 
  25. ↑ L'Heureux, M.L. (6 August 2018). "Testing for Pesticides and Mycotoxins in Cannabis: How to Meet Regulatory Requirements". Cannabis Science and Technology. UBM. https://www.cannabissciencetech.com/view/testing-pesticides-and-mycotoxins-cannabis-how-meet-regulatory-requirements. Retrieved 07 July 2021. 
  26. ↑ 26.0 26.1 "<561> Articles of Botanical Origin" (PDF). United States Pharmacopeia and The National Formulary. United States Pharmacopeial Convention. 1 July 2007. Archived from the original on 02 December 2017. https://web.archive.org/web/20171202221121/https://hmc.usp.org/sites/default/files/documents/HMC/GCs-Pdfs/c561.pdf. Retrieved 07 July 2021. 
  27. ↑ Association of Official Agricultural Chemists (9 October 2019). "AOAC SMPR 2019.001 - Standard Method Performance Requirements (SMPRs) for Detection of Aspergillus in Cannabis and Cannabis Products" (PDF). https://www.aoac.org/wp-content/uploads/2019/10/SMPR-2019_001.pdf. Retrieved 07 July 2021. 
  28. ↑ Cundell, T. (31 July 2015). "Microbiological attributes of powdered cannabis". American Pharmaceutical Review. CompareNetworks, Inc. https://www.americanpharmaceuticalreview.com/Featured-Articles/177487-Microbiological-Attributes-of-Powdered-Cannabis/. Retrieved 07 July 2021. 
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