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
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.
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.
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.
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.
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.