Certified Reference Material Manufacturing Challenges

November 12, 2018
Abstract / Synopsis: 

Some analysts will look at a list of pesticides or solvents and visualize adding small amounts of pure material of each analyte into a volumetric flask and then bringing the flask up to volume with their solvent of choice. In rare instances this technique will work, but not often. Prior to making a mixture, factors such as solubility and reactivity must be considered. Are all of the analytes soluble in the solvent that I want to use? Do I need to use an intermediate solvent? Will the analytes react with each other or will they react with the solvents? Do I need to add a preservative? Which preservative should I use and will any of the analytes react negatively to the preservative? The answers to these questions come from experience and a working knowledge of the chemistry of reference material (RM) production. Manufacturing the standard mixture is only the first step in creating a certified reference material (CRM). The CRM must be characterized using a metrologically valid procedure. A certificate of analysis is produced listing certified values for specified properties and all analytes, including a calculation of total uncertainty, homogeneity, stability under specified conditions, and metrological traceability. The certificate of analysis is delivered with the standard.

If you work in an analytical chemistry laboratory you may have heard the terms certified reference material (CRM) and reference material (RM). An RM typically comes with a certificate of composition (COC) that states the identity of the product, the purity of the product, and the details of its characterization. In addition to the information found in the RM COC, the CRM certificate of analysis (COA) declares that the material characteristics were determined by a metrologically valid procedure for the specified properties and contains a statement of metrological traceability, homogeneity data, long term stability results, and all factors that determine the CRMs total combined uncertainty, to name a few. This uncertainty includes the measured uncertainty inherently found in all measurement tools used in the manufacturing process as well as the effects of storage, transportation conditions, and possible chemical interactions affecting long term stability. 

The Benefits of CRMs

CRMs, as opposed to RMs, give labs a competitive advantage and peace-of-mind. ISO 17025 recommends that accredited labs use CRMs whenever available. As a laboratory, you can trust that everything has been done to provide you with a high quality standard that helps to ensure that your data can be generated correctly the first time, and every time. After all, the quality of your data can directly affect consumer safety. Because the use of CRMs helps to ensure data quality, your services are of greater value to your clients and prospective clients.

CRM Challenges

All CRM manufacturers strive for the lowest possible combined uncertainty during the manufacturing process. There are some variables that cannot be precisely controlled during the manufacturing process such as the limitations of Class A glassware (typically, the uncertainty at a specific temperature is written on the glassware) and syringes, precise room temperature, and the uncertainty inherent in all analytical balances despite calibration with National Institute of Standards and Technology (NIST) certified weights. The most challenging uncertainty to calculate is the uncertainty obtained from possible analyte to analyte and analyte to solvent interactions.

What Skills Are Needed to Create CRMs?

The first skill required when making a stock standard from a neat material is knowing which solvent is miscible or soluble with the analyte and if the analyte and solvent will quickly interact under the given storage conditions. If your working standard will be in a solvent different from your stock solvent, then the stock’s solvent is sometimes known as an intermediate. For example, if you want to spike used motor oil into water, you know that oil and water aren’t miscible. If you first dilute your oil with isopropanol at a reasonable concentration, the oil–isopropanol solution can be successfully spiked into the water matrix and you will have the used motor oil in solution with your water. The isopropanol is your intermediate solvent.