The Practical Chemist

Building the Foundation of Medical Cannabis Testing – Understanding the Use of Standards and Reference Materials – Part 2

By Joe Konschnik
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In the last article I referred to the analogy of the analytical reference material being a keystone of the laboratory foundation, the stone upon which all data relies. I then described the types of reference materials and their use in analytical testing in general terms. This article will describe the steps required to properly manufacture and deliver a certified reference material (CRM) along with the necessary documentation.

A CRM is an exclusive reference material that meets strict criteria defined by ISO Guide 34 and ISO/IEC 17025.  ISO is the International Organization for Standardization and IEC is the International Electrotechnical Commission. These organizations work together to set globally recognized standards. In order for a reference material to be labeled as a CRM it must 1) be made with raw or starting materials which are characterized using qualified methods and instruments, 2) be produced in an ISO-accredited lab under documented procedures, and 3) fall under the manufacturer’s scopes of accreditation. Verifying a CRM supplier has these credentials is easily done by viewing their certificates which should include their scopes of accreditation. Restek_accredit

There are many steps required to produce a CRM that meets the above three criteria.  The first step requires a review of the customer’s, or end-user’s requirements to carefully define what is to be tested, at what levels and which analytical workflow will be used.  Such information enables the producer to identify the proper compounds and solvents required to properly formulate the requested CRM.

The next step requires sourcing and acquiring the raw, or starting materials, then verifying their compatibility and stability using stability and shipping studies in accordance with ISO requirements. Next the chemical identify and purity of the raw materials must be characterized using one or more analytical techniques such as: GC-FID, HPLC, GC-ECD, GC-MS, LC-MS, refractive index and melting point. In some cases, the percent purity is changed by the producer when their testing verifies it’s different from the supplier label. All steps are of course documented.

restek_CRMThe producer’s analytical balances must be verified using NIST traceable weights and calibrated annually by an accredited third party provider to guarantee accurate measurement. CRMs must be prepared using Class A volumetric glassware, and all ampules and vials used in preparation and final packaging must be chemically treated to prevent compound degradation during storage. Next, CRMs are packaged in an appropriate container, labeled then properly stored to maintain the quality and stability until it’s ready to be shipped. All labels must include critical storage, safety and shelf life information to meet federal requirements. The label information must be properly linked to documentation commonly referred to as a certificate of analysis (COA) which describes all of the above steps and verifies the traceability and uncertainty of all measurements for each compound contained in the CRM. Restek_CRM2

My company, RESTEK, offers a variety of documentation choices to accompany each CRM. Depending on the intended use and data quality objectives specified by the end-user, which were defined way back at the first step, three options are typically offered: They include gravimetric only, qualitative which includes gravimetric, and fully quantitative which includes all three levels of documentation. The graphic to the right summarizes the three options and what they include.

It’s important to understand which level you’re purchasing especially when ordering a custom CRM from a supplier. Most stock CRMs include all three levels of documentation, but it’s important to be sure.

Understanding what must be done to produce and deliver a CRM sets it apart from other reference material types, however it’s important to understand there are some instances where CRMs are either not available, nor required and in those situations other types of reference materials are perfectly acceptable.

If you have any questions or would like more details about reference materials please contact me, Joe Konschnik at (800) 356-1688 ext. 2002 by phone, or email me at joe.konschnik@restek.com.

The Practical Chemist

Building the Foundation of Medical Cannabis Testing – Understanding the Use of Standards and Reference Materials – Part 1

By Joe Konschnik
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In previous articles, you may recall that Amanda Rigdon, one our contributing authors, stated that instrument calibration is the foundation of all data quality. In this article, I would like to expand on that salient point. A properly calibrated instrument will, in fact, produce reliable data. It is the foundation we build our data upon. All foundations are comprised of building blocks, and our laboratory is no exception. If we take this analogy further, the keystone to the laboratory foundation, the stone that all data relies upon, is the analytical reference material. Proper calibration means that it is based on a true, accurate value. That is what the reference material provides. In this article, I would like to expand on the use and types of reference materials in analytical testing.

To develop sound analytical data, it is important to understand the significance of reference materials and how they are properly used. The proper selection and use of reference materials ensures the analytical certainty, traceability and comparability necessary to produce scientifically sound data. First, let’s take a moment to define the types of commonly used reference materials. According to the International Vocabulary of Metrology (VIM), a Reference Standard (RS) is something that is reused to measure against, like a balance or a set of weights. A Reference Material (RM) is a generic term. It is described as something that is prepared using a RS that is homogeneous, stable and is consumed during its use for measurement. An example of an RM is the solutions used to construct a calibration curve, often referred to as calibration standards, on your GC or LC. Due to the current state of cannabis testing, reference materials can be hard to find and, even more critical, variable in their accuracy to a known reference standard. Sometimes this is not critical, but when quantifying an unknown, it is paramount.

RMs can be either quantitative or qualitative. Qualitative RMs verify the identity and purity of a compound. Quantitative RMs, on the other hand, provide a known concentration, or mass, telling us not only what is present, and its purity, but also how much. This is typically documented on the certificate that accompanies the reference material, which is provided by the producer or manufacturer. The certificate describes all of the properties of the starting materials and steps taken to prepare the RM. For testing requirements, like potency, pesticides, etc., where quantitation is expected, it is important to use properly certified quantitative RMs.

Now, the pinnacle of reference materials is the Certified Reference Material (CRM). VIM defines a Certified Reference Material (CRM) as an RM accompanied by documentation issued by an authoritative body and provides one or more specified property values, with associated uncertainties and traceability using valid procedures. A CRM is generally recognized as providing the highest level of traceability and accuracy to a measurement – the strongest keystone you can get for your foundation. It is also important to recognize that the existence of a certificate does not make a reference material a CRM. It is the process used in manufacturing that makes it a CRM, and these are typically accreditations earned by specific manufacturers who have invested on this level of detail.

Now that we understand the types of reference materials we can choose, in the next article of this series we will describe what a CRM provider must do to ensure the material and how we can use them to develop reliable data. Without properly formulated and prepared CRMs, instrument calibration and the use of internal standards are less effective at ensuring the quality of your data.


If you have any questions please contact me, Joe Konschnik at (800) 356-1688 ext. 2002 by phone, or email me at joe.konschnik@restek.com.