“There are known knowns. These are things we know that we know. There are known unknowns. That is to say, there are things that we know we don’t know. But there are also unknown unknowns. There are things we don’t know we don’t know.”
Truer words have not likely been spoken in the world of analytical chemistry when it comes to Synthetic Cathinones and Synthetic Cannabinoids.
We have blogged before on this subject: More on the forensics of synthetic drugs: synthetic cannabinoids and synthetic cathinones
I wrote in that post:
The forensic world continues to grapple with the forensics of identifying synthetic drugs and their pharmacological and analytical chemistry characteristics. As we have written before just because there may be laws on the books or emergency or permanent regulations outlawing certain drugs and their analogues doesn’t mean that they can actually prove scientifically that the unknown substance that is seized and submitted for testing is actually the listed controlled substance and that the reported qualitative measurement (what is it?) is in fact specific (meaning it is that one substance and that one substance alone to the exclusion of every thing else). If the government cannot prove the validity of the qualitative measurement beyond a reasonable doubt, then there can be no conviction. Further in impaired driving prosecutions, if it cannot be proven that the drug actually exists in the blood because the analyst’s opinion as to the qualitative measurement is not valid, then there can be no conviction. Further, in the case of an impaired driving based prosecution, we do not have information that would allow a pharmacologist to opine impairment based upon an analytical chemistry result alone.
The import distinction between standards/controls and true certified reference materials (CRMs or NIST SRMs) can be read about generally here: Standards, Controls, Calibrators, and Verifiers, Oh my…
To earn the legitimate moniker of CRM/SRM, the standard/control must satisfy the ISO Guide 30-35 protocols.
- ISO Guide 30:1992 (REMCO) Terms and definitions used in connection with reference materials
- ISO Guide 30:1992/Amd 1:2008 (REMCO) Revision of definitions for reference material and certified reference material. This guide recommends terms and their meaning used in connection with reference materials, taking into account those terms which are used in reference material certificates and appropriate test reports.
- ISO Guide 31:2000 (REMCO) Reference materials — Contents of certificates and labels. This Guide is intended to help producers to prepare clear and concise certificates to accompany certified reference materials. Such certificates, while maintaining their essential character, should help to provide, in summary form, all the information needed by the user of the reference material.
- ISO Guide 32:1997 Quality assurance in a testing laboratory, particularly in the case of its assessment (see ISO/IEC Guide 25), highlights the need to consider closely the question of the accuracy of its measurements and analytical results, and to ensure that the principles necessary to establish demonstrated accuracy have not been omitted. The calibration of the parameters associated with chemical analyses and material testing deserves particular attention, because major errors can be made by neglecting or ignoring the basic principles of metrology which also apply to these areas. This Guide identifies a number of general recommendations for those who, either in laboratories or as assessors, are faced with this problem.
- ISO Guide 33:2000 (REMCO) Uses of certified reference materials. This Guide discusses the uses of certified reference materials (CRMs) and their correct applications. Clause 2 of this Guide presents definitions (with indication of their sources) of terms used, and clause 4 sets out the statistical considerations on which the Guide is based. Clause 5 discusses the role of CRMs in measurement science and in realization of conventional measurement scales. Clause 6 presents recommendations for developing criteria for the assessment of the precision and trueness of a measurement procedure by the use of CRMs. It pertains only to CRMs characterized to be homogeneous as described in ISO Guide 35.
- ISO Guide 34:2009 (REMCO) General requirements for the competence of reference material producers. Guide 34:2009 specifies general requirements in accordance with which a reference material producer has to demonstrate that it operates, if it is to be recognized as competent to carry out the production of reference materials. Guide 34:2009 is intended for the use by reference material producers in the development and implementation of their management system for quality, administrative and technical operations. Reference material customers, regulatory authorities and accreditation bodies may also use it in confirming and recognizing the competence of reference material producers. Guide 34:2009 is not intended to be used as the basis for conformity assessment by certification bodies. Guide 34:2009 sets out the management system requirements in accordance with which reference materials shall be produced. It is intended to be used as part of a reference material producer’s general quality assurance (QA) procedures. Guide 34:2009 covers the production of certified and non-certified reference materials. For non-certified reference materials, the production requirements are less stringent than for certified reference materials. The minimum requirements for the production of non-certified reference materials are specified throughout the Guide.
- ISO Guide 35:2006 (REMCO) Reference materials — General and statistical principles for certification. ISO Guide 35:2006 gives statistical principles to assist in the understanding and development of valid methods to assign values to properties of a reference material, including the evaluation of their associated uncertainty, and establish their metrological traceability. Reference materials (RMs) that undergo all steps described in ISO Guide 35:2006 are usually accompanied by a certificate and called a certified reference material (CRM). This Guide will be useful in establishing the full potential of CRMs as aids to ensure the comparability, accuracy and compatibility of measurement results on a national or international scale. In order to be comparable across borders and over time, measurements need be traceable to appropriate and stated references. CRMs play a key role in implementing the concept of traceability of measurement results in chemistry, biology and physics among other sciences dealing with materials and/or samples. Laboratories use these CRMs as readily accessible measurement standards to establish traceability of their measurement results to international standards. The property values carried by a CRM can be made traceable to SI units or other internationally agreed units during production. ISO Guide 35:2006 explains how methods can be developed that will lead to well established property values, which are made traceable to appropriate stated references. It covers a very wide range of materials (matrices), ranging from gas mixtures to biological materials, and a very wide range of properties, ranging from chemical composition to physical and immunoassay properties.
A very good summary can be found here: EA 04/14: The Selection and Use of Reference Materials
At this past American Academy for Forensic Sciences annual meeting, I was able to talk to all of the major standards makers in the world. This is a report based upon my conversation with them:
- Agilent-we are working on it, nothing now
- Sigma Aldridge-we are working on it, nothing now
- Restek-we are working on it, nothing now
- NIST- we are working on it, nothing now. However, they do offer an update to the NIST spectral library that includes several of these drugs for EI-based MS Q
- DEA-we synthesize our own in our labs or certify seizures but not according to ISO Guide 30-35 and it is not available for distribution outside of the DEA and only minimally then within the DEA. So it is not commercially available. They characterize them as standards, not SRMs/CRMs.
- NMS-we synthesize our own in our labs or certify seizures but not according to ISO Guide 30-35 and it is not available for distribution outside of NMS. So it is not commercially available. They characterize them as standard, not SRMs/CRMs.
- Cayman- here is the literature from their website for synthetic cannabinoids, and synthetic cathinones. I had a long talk with their chief scientist/chemist. They synthesize the materials in-house. These products are commercially available standards. They frankly admit they are not ISO 17025 lab. They also do not certify these per ISO Guide 30-35. When asked about the validity of their qualitative identification of the product they synthesize, he basically said “we’re really good chemists.” He acknowledges the lack of them being an ISO 17025 lab and not following ISO 30-35 as a “problem they are working on.” They even also offer metabolites for these drugs. When asked how they came to the conclusion that what they offer were valid, he confessed they were theoretical as both he and I knew there were no pig models yet published on these metabolites. They characterize them as standard, not SRMs/CRMs. Scary stuff.
Other posts included:
- Can (insert analyte) be tested for by GC-FID or GC-MS?
- DEA Moves to Emergency Control Synthetic Stimulants
- New Designer Drugs Pose a Problem for Forensic Science
- Pennsylvania Bans Bath Salts and Synthetic Marijuana
- Bath Salt Laws in PA
- PA DUI Drugs Update: K2 Banned by DEA
- Dear PA DUI Attorney: Can You Land a DUI for Synthetic Marijuana?