The great reagent arms race

Keeping pace with the demands of sophisticated instrumentation can be an uphill battle thinks Anthony Lenk as he discusses the origin and evolution of today’s chemical standards

The relationship between analytical techniques and solvents can be compared to that of computers and software. One complements the other; the performance of the software must equal that of the computer to obtain the best results. The same can be said of analytical techniques and solvents, as the quality of the results is highly dependent on the purity of the solvents used. With existing technology continually improving and new innovations coming to the marketplace, the need for exceptionally high-quality solvents has never been greater and manufacturers must rise to the challenge.

Much of the early development of analytical chemistry took place in Germany, including the 1888 landmark publication of The Testing of the Purity of Chemical Reagents¹ by Dr Carl Krauch, a chemist employed by Merck, which described standards and tests for analytical reagents. Shortly afterwards, the company introduced a range of some 150 ‘analytical reagents’ meeting these chemical standards of purity. Krauch’s book represented a significant milestone in the drive to establish standards of chemical purity and, in 1902, it was translated into English by J.A. Williamson, chief chemist at British company Baird & Tatlock. Such was its popularity that it is still available today², enabling scientists to continue to benefit from Krauch’s ideas.

Post-war chemicals Germany was the major provider of analytical reagents to the UK until the outbreak of World War 1, when the supply ceased abruptly. In Britain, the response was to set up a joint committee, appointed by the Institute of Chemistry and the Society of Public Analysts, to find a way to resolve the problem. By 1915, the committee had published the List of reagents for analytical purposes, with notes indicating the standards of purity regarded as necessary for analytical work³. These chemicals were designated ‘AR’ grade, signifying an analytical reagent of guaranteed purity.

Across the Atlantic, the American Chemical Society instigated the ACS standard, which is still in use today

Post war, with Germany no longer the dominant chemical supplier and demand for reliable analytical reagents still growing, both Britain and America continued to develop specifications to meet the requirements of the analytical techniques of the time. Two British firms, British Drug Houses – more recently known as BDH – and Hopkin & Williams, went on to establish what eventually became known as AnalaR grade chemicals, defining the standards of purity in ‘Analar’ Standards for Laboratory Chemicals⁴. This joint publication provided a record of the main properties of the substances and described how the purity was checked, becoming a useful reference manual for both qualitative and quantitative analysis. Across the Atlantic, the American Chemical Society instigated the ACS standard, which is still in use today.

Reagent arms race Technology never stands still, and analytical techniques developed very rapidly after the Second World War. The introduction of new specialist techniques with continually improving detection levels brought an ever-increasing need for enhanced solvent purity to meet the demands of sophisticated modern instrumentation. Much is said about the sensitivity and detection capabilities of the latest analytical techniques, but the systems are only as good as the solvents that are used with them. For the highest quality results, the performance of the solvents must match that of the instrument, and it soon became clear that analytical grade reagents that were suitable for older techniques were no longer pure enough for new and more sensitive methods. With the advent of hyphenated techniques, the situation became even more complex; LC-MS analysis, for example, requires not only extremely high purity solvents, but also excellent batch-to-batch consistency for reliable, reproducible results. Frequently, scientists would find themselves distilling solvents in the laboratory in an attempt to enhance the purity because analytical grade solvents, which had been more than adequate in the past, were no longer of sufficiently high quality for use with modern, state-of-the-art analytical instrumentation.

A situation developed where each time a new technique was launched, or a different specification was required, manufacturers would simply introduce another reagent grade. The result was a confusing array of reagent grades – HPLC, spectroscopy, UV, etc – and purity levels targeted to particular techniques. Scientists might have as many as 12 different grades of methanol to choose from, for example, and it was not always easy to select the correct one.

Scientific afterthought? The majority of laboratory chemicals are manufactured with industrial applications in mind, rather than the chemical laboratory; acetonitrile, for example, is produced as a by-product of acrylonitrile and requires secondary purification before it can be used with sensitive analytical instruments. As a consequence, the laboratory sector accounts for a very small proportion of the manufacturer’s output, and there is little interest in producing chemicals specifically for this purpose. This can cause problems for analytical laboratories. The impact of cleaning a production plant or replacing spent catalyst, for instance, will pass unnoticed by industrial customers, yet this can have a profound influence in the laboratory, significantly affecting the quality of the analytical results.

However, while the solvent may be optically pure and appear clean to the naked eye, it is likely that a considerable non-volatile residue will have been accrued during shipping

The reality is that solvents are sourced from a limited number of specialist chemical companies, and one product may be marketed under many different brands. In many cases, solvents are batch selected. Suppliers simply test each batch for suitability on delivery, and then repackage it into smaller containers for laboratory use; one batch may well serve a multitude of solvent grades. However, while the solvent may be optically pure and appear clean to the naked eye, it is likely that a considerable non-volatile residue will have been accrued during shipping. This can be problematic in the laboratory causing, for example, blockages in HPLC lines, pumps and columns. A good supplier will insist that solvents undergo extensive purification by chemical treatment and glass distillation, significantly reducing impurities and enhancing batch-to-batch consistency, minimising unnecessary downtime and the need to troubleshoot ghost peaks. The result will be a single grade product suitable for a range of techniques, eliminating much of the confusion surrounding the choice of solvent, and helping to ensure reliable, reproducible results.

Science never stands still, and the continual development of new technologies and analytical methods drives the ongoing demand to constantly enhance standards of solvent purity. Laboratory chemical suppliers must now build on the successes of the past, rising to the challenge of keeping pace with future scientific innovations by producing solvents of exceptional purity to meet the exacting requirements of ever-more sensitive instrumentation.

Author: Anthony Lenk is Director of laboratory chemical manufacturer ROMIL

References: 1. Krauch, C. Die Prüfung der chemischen Reagentien auf Reinheit (The Testing of the Purity of Chemical Reagents). 1988. Pub: L. Brill, Darmstadt. German. 2. Krauch, C, Dupré, LW, Williamson, JA. The testing of chemical reagents for purity. 2017. Pub: ReInk Books. 3. List of reagents for analytical purposes, with notes indicating the standards of purity regarded as necessary for analytical work. 1915, 39. Proc. Inst. Chem. GB Irel. 4. ‘Analar’ Standards for Laboratory Chemicals: being improved standards for the analytical reagents formerly known as ‘AR’. 1934. The British Drug Houses Ltd. and Hopkin & Williams Ltd., London