The Future of Dioxin and Dioxin-like Compound Analysis - Moving Past Magnetic Sector Instruments

Frank Dorman | Waters Corporation

Is Dioxins analysis in trouble? Will HRMS be phased out? What does the future hold for analysis using magnetic-sector instruments?  Frank Dorman, Senior Principal Environmental Market Manager at Waters, explores these questions. 

The History: 

For decades, the standard analytical methodology for the analysis of dioxins and related compounds relied upon gas chromatographic separation (GC) coupled to high resolution mass spectrometry (HRMS) employing magnetic sector mass spectrometers. This technique was one of the rare regulatory cases where GC-HRMS was the analysis of choice and applied to environmental, food, industrial, and other fields.  During the 1980’s and 1990’s there were refinements in the size and complexity of operation for these large (relative to modern mass spectrometers with different geometries) instruments. As observed in the image below, the Waters/Micromass AutoSpec represented an industry-leading instrument into the 2000’s, but over the last decade or more, interest in the continued use of these systems has been declining. 

Why has the interest in the Waters/Micromass AutoSpec decreased? 

Well to put it simply, operation of these systems is relatively demanding on operator experience.  These instruments tend to have a large “personality” and the operators need to spend time and effort building a relationship with these systems to successfully operate them at the highest levels of performance. Additionally, the cost and availability of some materials used in the manufacturing of these instruments have become more challenging and as a result, there are very few places where they can be purchased.  Lastly, service has become more challenging as some of the former manufacturers have dropped these instruments from their current portfolios. 

Is dioxins analysis in trouble? 

It is an interesting question! Laboratories that are required by regulatory bodies to perform the analysis using magnetic-sector instruments face increasing challenges as they struggle to maintain workload on aging instruments. Additionally, servicing of their existing instruments has become more difficult as qualified service representatives decrease in number and some instruments currently in use are no longer supported through service contracts, due to availability of parts. Also, commercial laboratories would prefer that their instruments be less demanding with regard to operator experience, as it is obviously desirable to be able to train analysts to perform high-quality work without having to essentially apprentice with a senior operator for quite some time as an instrument’s personality becomes well understood. Demanding operator experience creates operators who are highly specialized on this particular instrument which impacts a laboratories’ ability to be flexible with staff as various sample requests fluctuate. This instrument inhibits the ability to have an adaptable staff and efficiently meet the current laboratory demands at any given time period.  Essentially, these instruments will be phased out of commercial laboratory dioxins (and related compounds) analysis, it is just a matter of when this occurs. 

What does the future hold in store? 

Luckily, there are options. Firstly, most regulatory methods encompass some sort of “performance-based” intent or language that technically allows laboratories flexibility regarding how they perform an analysis as long as it meets the quality objectives of the written method. For example, it might be relatively common for dioxin laboratories to incorporate different adsorbents for extract cleanup. Various types and specifications for carbon are common with no single source of carbon being used for all labs world-wide that perform this analysis.  The reverse-elution carbon fractionation is a common step, but the specific material that is used will vary from lab-to-lab and with respect to what is mentioned in the original regulatory method. 

While this type of change is common, instrumental modifications are less so. That doesn’t mean that the regulatory methods absolutely do not allow for adaptation, however, it just may be onerous for laboratories. The USEPA, for example, has a procedure for laboratories to submit an alternate test procedure (ATP) that can allow for instrumental adaptations and other methodological changes to be officially allowed for regulatory compliance.  For dioxins analysis, one such ATP was successfully submitted and accepted in September of 2020 by SGS-AXYS [1]. Known as “SGS-AXYS Method 16130”, this enables laboratories to utilize tandem quadrupole MS/MS as a replacement for HRMS for Method 1613 analysis of wastewater. 

Other techniques have been evaluated, such as Quadrupole coupled to Time-of-Flight (QToF) mass spectrometry and other, non-magnetic sector-based mass spectrometers, but the tandem quadrupoles are clearly the path forward.  In short this is due to their sensitivity, linearity and more simplistic operation as compared to other options.  For these targeted regulatory methods, they are the clear choice, and to date, no negative bias of tandem quadrupoles compared to HRMS has been reported for dioxins analysis. 

OK, so it’s simple then, right? 

Not so fast. While MS/MS with tandem quadrupoles is going to replace the HRMS for dioxins and related POP’s analysis, the customer base has been slower to adopt.  Effectively, the customers of the commercial laboratories are sometimes skeptical of proposed methodological changes, even if the regulatory agency has accepted them. Since the customers have the ultimate decision, many have merely requested that the laboratory not change anything based upon fear of the unknown. “Why change what isn’t broken”, they may feel. As a result, a number of manufacturers of tandem quadrupoles are finding it more challenging to replace what the scientific community and the commercial laboratories know is coming.  

Customers do not realize that if they do not adapt to this increasing necessity, the day may come when they can’t get their analysis performed as they have historically been able to, and change will be forced upon them. It is always better to transition into change rather than be smacked with it when you may find it less than an ideal time. Being proactive is always better than being reactive, and the cards are clearly stacked against HRMS for the future of commercial dioxins analysis. Tandem quadrupoles are much more common, easier to operate, and offer selectivity in multiple reaction monitoring (MRM) mode that rivals the HRMS for this work.  

Additionally, with an atmospheric pressure ionization (API) source, tandem MS/MS has been demonstrated to far outperform HRMS and electron-ionization MS/MS as far as sensitivity. This opens the possibilities of sample preparation modification to further increase laboratory throughput without a negative impact to data quality.  With “standard” sample preparation, API-MS/MS allows for significantly improved reporting limits, and this has been described in many publications over wide-ranging sample matrices. 

So, what about the future? 

Laboratories should consider being proactive with this one. The adoption of MS/MS into traditional HRMS laboratories will be better if carried out in a controlled manner, rather than waiting until HRMS is no longer available/supported. It should be a priority to gain operator experience sooner and develop operating procedures now, while the HRMS’s are still in operation. Laboratories should also validate the new methodology and gain acceptance from the customer base in an organized way.  It may even be beneficial to provide data from both techniques so that the customer base gains comfort and feels included in the decisions to move to MS/MS. 

For the customers, if you are reading this blog, the change is coming. MS/MS will initially be an option along with HRMS, but it is the author's prediction that once it gains a bit more visibility, HRMS will be phased out.  Maybe rather quickly, leaving the holdouts with no options left but forced change. This is a technique with well over a decade of commercial operation and it has clearly excelled. Regulatory agencies are poised to give formal acceptance and ATP’s are currently allowed. Make the change now when data can be run with both techniques and give yourself, and your clients, the comfort that the move to MS/MS is not only wise but also brings benefits with it like multiple compound class analysis, improved reporting limits, increased instrument robustness, and a platform that is easily mastered by the analysts in the commercial laboratories. 

MS/MS is the future, and the future is here! 

#Dioxins #GCMS #HRMS #Waters4APGC #Sustainability

Reference: 

1. https://www.epa.gov/cwa-methods/methods-measurement-2378-substituted-tetra-through-octa-chlorinated-dibenzo-p-dioxins