FUJIFILM Wako Pure Chemical Corporation, Tokyo plant

Production of CRM (certified reference material) using ISO24583 (qNMR method) started, first in the world^※1

qNMR (quantitative NMR) method has been a Japan Industrial Standards (JIS), and an International Organization for Standardization (ISO).The ISO (international Organization of Standard) for qNMR method was established through the collaboration research by five organizations including FUJIFILM Wako Pure Chemical Corporation and JEOL Ltd. FUJIFILM Wako Pure Chemical Corporation provides reference material and certified reference material (CRM) that are required for this analytical method, as well as performs quality control for their own product.

^※1 As of October 30th, 2023

First Breakthrough Analytical Method In 100 years

"It is not possible to use NMR to measure the purity". Yuko Yamada, Senior Manager, FUJIFILM Wako Pure Chemical Corporation (Quality Control Department, Tokyo plant, Production Management Operations, Laboratory and Specialty Chemicals Division,) believed so, at first.

She was aware that the NMR can be used to assume the concentration and purity. However, the accuracy mattered. The position of the Quality Control Department is to analyze and evaluate the reagents and chemicals before shipment and assure their component. Depending on the assurance level, a method is not considered applicable unless it can perform analysis with an accuracy of about 1% or better. With Ms. Yamada's awareness, NMRs can perform analysis with an accuracy of about 5% or so at the maximum. So, it was chromatography that was most used at the analysis site.

However, chromatography requires a reference material of known purity that is identical to the analyte. Thus, it is not applicable for the target for which no reference material has been available such as new drugs. Ms. Yamada once had an experience of obtaining purity by a method other than chromatography, when she was in charge of analysis of medical and investigational drugs. The process was so complicated, and she thought that "if only NMR could be used and make it simpler," and "if it could be done, it would be the first great analytical method since chromatography in 100 years".

As a matter of fact, no reference material for chromatography was available or easy to obtain for food sanitation and many other fields. This situation has increased gradually. New organic compounds were produced every day and the number of analysis target analytes increased. It was difficult to provide individual reference material for all of them, time-wise and cost-wise.

NMR accuracy improved through collaboration research.

In 2008, a collaboration research was launched to aim for practical use of quantitative analysis using NMR by five institutions^*2, in an attempt to find new analysis methods to deal with the situations like this.

Note ^*2 Five institutions: National Institute of Health Sciences, Independent Administrative Agency of Advanced Industrial Science and Technology (AIST) (now: National Institute of Advanced Industrial Science and Technology (AIST)) , Kao Corporation (joined in 2009), Wako Pure Chemical Industries, Ltd. (now: FUJIFILM Wako Pure Chemical Corporation), and JEOL Ltd.

The collaboration research began producing the outcomes gradually. Accuracy gradually improved as the measurement and analysis conditions were optimized and the software was tuned accordingly. Seeing this progress, Ms. Yamada was convinced, "This is going to work. A new analysis method that she had longed for in 100 years was in sight.

And qNMR has proceeded with a standardization. It became a Japan Industrial Standard (JIS) in 2018^*3, and in 2022 it was issued as an International Standardization Organization (ISO)^*4.

Note ^*3 JIS K 0138 : 2018 General rules for quantitative nuclear magnetic resonance spectroscopy

Note ^*4 Quantitative nuclear magnetic resonance spectroscopy -- Purity determination of organic compounds used for foods and food products -- General requirements for 1H NMR internal standard method

There are many advantages at the analysis site

FUJIFILM Wako Pure Chemical Corporation is a supplier of reference material and certified reference material for qNMR. The reference material for qNMR is not the identical substance as the target analyte, which is the case with chromatography. The reference material is mixed and measured with the target analyte for further reference in measuring the quantity. One reference material/certified reference material can be used for a number of measurement target materials. However, it is important that the measurement target does not have the same NMR spectrum as the target material and it would be convenient if more than one choice is available as solvent can matter. In the future, they plan to prepare hundreds of reference materials/certified reference materials.

Since Certified Reference Material (CRM)s are standard substances that are traceable to international system of units (SI), they are used to improve the reliability of obtained analysis values and provide international consistency. FUJIFILM Wako Pure Chemical Corporation is now able to produce the CRM by a method with flexible accreditation, instead of obtaining a separate accreditation.

FUJIFILM Wako Pure Chemical Corporation is promoting dissemination of qNMR methodology, but they are also users of the NMR on the other hand. The Quality Control Department has three NMRs for qNMR analysis. In October 2023, they have replaced one NMR with the latest model of JNM-ECZL400S which has automation capability. As they are planning to increase evaluation works using qNMR, the replacement is to promptly and efficiently handle many measurement target materials according to them.

They have already replaced the evaluation method for many items with qNMR. For example, the company distributes about 1000 pesticide residue analysis standards and they replaced about 700 items among them with analysis by qNMR for quality assurance. The reliability of the value by qNMR is high and it has little adjustment for measurement and shorter measurement time, compared with chromatography. They seem to realize that it is an analytical method which has many advantages at analysis site.

FUJIFILM Wako Pure Chemical Corporation is hoping to satisfy various users' needs, by preparing a complete supply system that not only provides a sufficient number of RMs/CRMs, but is also able to promptly provide them to meet new requests.

JEOL Products

FUJIFILM Wako Pure Chemical Corporation

Quantitative NMR (qNMR)