Method Flexibility and the March 12, 2007 Method Update Rule

Method Flexibility and the March 12, 2007 Method Update Rule


The USEPA wet chemical methods that are approved at 40 CFR Part 136 are for the most part really determinations and not analysis (CO Ingamells and Francis Pitard “Applied Geochemical Analysis” page 191). By this I mean that they are attempting to identify trace amounts of analyte within the matrix with almost no preliminary separation. The methods are written including, not only the reagents needed to create a final measurable product, but also complex reagents and buffering reagents formulated to adjust pH and prevent interferences from occurring. It is impossible for one method, or one set of conditions to work on every matrix. Since wastewaters are so complex, wastewater methods must allow users to modify methodology to work on their samples.

Rapid chemical methods, with as few steps as possible, are the only way thousands of samples can be analyzed by semiskilled or unskilled analysts. A rapid method performs well in the matrix it was tested assuming it is followed exactly.

So why do we have method flexibility? We have it because we asked for it. The ability to modify a method has been embedded in the QA/QC section of various methods and has gone under the ‘title’ of performance based for years. Later, method flexibility was added to 40 CFR as Part 136.6. Reasons to modify a method range from the change of one instrument to another to removal of matrix interferences.

Rapid Chemical Methods and Environmental Testing

Most countries have adopted rapid chemical methods for use in environmental regulations. The logic is that there is a maximum allowed limit for a toxin and we will measure it. Large sums of money are invested by industry and government agencies based on the numerical results of these methods. Because the methods are promulgated, the results whether right are wrong, determine compliance. Not following the SOP will place you out of compliance simply for not following the SOP word for word.

I have written numerous articles about total cyanide by distillation. It is possible to analyze total cyanide in a sample, get a positive result, get fined for releasing cyanide and cyanide not actually be there. A simple modification of the approved method reports the correct result, however, previously modification of the method was considered a violation even if the modification produced the correct result.

In many cases following the SOP is OK, however, without modifying methods to handle as many interferences as possible you will never know. Total cyanide is interesting because the distillation generates the cyanide. Spike recoveries and duplicates will be acceptable, even though cyanide is not really there.

Approval letters and the Alternative Test Procedure

So why add method flexibility to the CFR? There are Alternative Test Procedures (ATP) that need to be properly evaluated so that these procedures can be promulgated. A method that simply modifies an approved method is not an ATP.

The EPA ATP coordinator was overwhelmed with requests for approval of discrete analyzer methods. Previously, this so called approval occurred as approvals of powder pillows, and Flow Injection instead of Segmented Flow. Part 136.6 allows users and method generators to change methodology without EPA review or rule making, providing the minimum criteria is met.

If you look closely at the wording of these “approval” letters, they are not approvals at all, but an acknowledgement by EPA the method in question is essentially equivalent to the approved one. EPA decided that the ATP coordinator’s time was better spent is pursuit of approving new alternative test procedures than it was with providing instrument manufacturers with letters to use as marketing material. The clincher of the deal was pretty much the discrete analyzer, which is essentially a new way to add reagents to samples and does not really change the methodology at all.

Another reason for method flexibility is the rigidity of the SOP. The earlier EPA methods were written under the assumption that chemists would use them. Over the years, as we are all aware, they became less used by chemists and more by lawyers. The mindset of following the SOP word for word developed and has reached a turning point. As we attempt to measure lower levels, we have to be able to adapt our current methods to allow us to see these lower levels. Not allowing a 25-milliliter purge volume because the method only says five milliliters, or not allowing capillary columns because the method calls for a packed column is silly and slows progress. There is not enough time, and certainly not enough of us, to revalidate every single method for every foreseeable change. We must allow experienced users to adapt existing methods to serve modern purposes.

Inability to Alter a Method Hampers Progress

There are thousands upon thousands of potential matrices and in them an infinite supply of potential things that can cause a method to not work. The method developer attempts to compensate for everything but this is not possible. What do we do about emulsions, or foaming, or suppression of the analyte? What do we do when we know that the approved procedure generates bias and we are reporting the wrong results? If our purpose is protecting the environment, are we really protecting it by generating bad data? What is the fraud, generating bad data by following the method, or not following the method and obtaining the correct result? Is it correct to modify one extraction to overcome interference, and then not carry out the whole process on every single sample? Is it correct to flag data as QC failed, but accept it because an LCS passed?

The better answer would be that all of our methods work perfectly on every sample. We can assure this by allowing experienced chemists to modify methods while ensuring that basic performance criteria are met. If a modification, such as changing a complex reagent, results in every sample obtaining results closer to the true value isn’t that better than flagging 10{4b1fe63123713d31487550d3441c07e511f9c896d21719779d3ce493da6269bd} of them? It is time to put some chemistry back in chemical analysis. We are not implying a blatant and random disregard for the SOP. We are saying that the data needs to matter more than the SOP. It is harder to modify and document an existing method to overcome interferences than it is to just follow the SOP. The criteria are not easy and assume that interferences are identified, characterized, and analyzed.

The Purpose of Method Flexibility

The purpose of method flexibility is to improve quality control. The purpose is to get better data. The purpose is to not have data qualifiers. The purpose is to allow you to overcome interferences. The end result should be the right result. One method cannot work on every single matrix. It is just not possible. Method flexibility is improvement.

These are reasons to modify methods. We can improve accuracy and precision, we can get better method detection limits (MDL), we can compensate for interferences, we can increase throughput, we can use “green reagents” and we can encompass the analytical range actually needed. These things can be done, but only by modification of existing methods. There is not the time, nor the resources, to revalidate every single method after making minute changes. If we change a buffer reagent, for instance, why not just demonstrate that the new buffer performs equally, or better, than the old one?

The criterion of a 40CFR part 136.6-method modification is equivalency of results. In other words, do you get the same result before and after a modification? The point is, however, that these equivalent results are obtained on data of samples without interference. In a way we are comparing apples and oranges. We can’t just be creating more apples. We want our new method to perform better than the old one.

Proof of Equivalency

To demonstrate equivalency, or illustrate what is different, the method generator prepares a two-column comparison between the approved method and the new one. For most items, such as scope, detector, and so forth the language will be the same. For method flexibility, the differences will be throughput, instrument, column, volumes of sample, and some of the reagents as long as 136.6 criteria is met.

The most important aspect of method modification is that QC criteria are met. The QC must meet or exceed the criteria given in the approved method. If you obtain certain MDL’s and response factors with a 30-minute cycle time, do you obtain similar data when the time is shortened? If you reduce a volume from 500 ml to 50 ml, is the precision the same?

Method flexibility gives us, for the first time in a long time, the opportunity to make those changes to methods that we know need to be changed. We can modify pH, or complex reagents, or buffers, and even some reagents for the purpose of getting better data. We can automate a manual method without getting a permission letter. 40 CFR part 136.6 should be viewed as a good thing.


In trace analysis, the analyte is present at very small quantities in relation to the rest of the sample matrix. It is literally looking for the needle in a haystack. A rapid chemical method looks for the needle without removing the hay. Lowering the MDL is similar to looking in even more hay for that one needle. At the same time, we want to find it faster, and with the least expense. Of course to use this analogy with accuracy and precision, or range we end up looking for multiple needles in the same haystack.

(Our calibration standards or QC samples, prepared in pure solvent, are looking for a little bit of something in a whole lot of nothing, while our samples contain a little bit of something in a whole lot of something else.)

Method flexibility is needed because method developers cannot foresee every potential interference or anticipate all matrices in which the method might be applied. Blindly following a method that is not working strictly to stay “in compliance” defeats the purpose of the measurement-that is, to obtain the correct result, not just to follow the method. Remember, that not all instruments are the same. A method developed on one instrument may require slight modifications to work on another. This is especially true when changing the analytical technique. Method flexibility should allow us to change to less toxic reagents and still measure the same final product. Thus, we could actually do our monitoring with “green” chemistry instead of using toxic chemicals to monitor for toxic chemicals.

I believe that 40 CFR Part 136.6 method flexibility is the light at the end of the tunnel. Finally we are not bound to follow rigid SOP’s. You can alter your instruments and methodology so that you obtain accurate, reliable results in a cost effective manner. This is not about shortcuts. This is about being scientific, once again. The analysis is all about the data. It has to be defensible, but it also needs to be correct. I realize that the commercial laboratory is hard pressed with time and resources to do their own modifications. This is why the burden of proof is on the instrument manufacturer. It is in the manufacturer’s best interest to make sure instrumentation and methodology works for its intended purpose. It is in the manufacturer’s best interest to work closely with EPA to verify that our method modifications are acceptable. The manufacturer will collect the data, and will provide all necessary information proving, not acceptance, but equivalence according to the CFR.