Analytical Method Authoring: Ensure that your Method is User Friendly for Quality Control- Part 1

As an HPLC analytical method development veteran, I know that we all have a way that we like to write methods that make sense to ourselves.  However, it’s very important to keep the end user of your “product”, the method, in mind.    Since methods have quite a few sections, I will discuss this over several blog posts, targeting methods validated for Phase 1 and Phase 2.

It’s important to put yourself in the shoes of the QC analyst and think about the environment in which they work.  It is a highly regulated environment with paperwork burying consequences if a method deviation occurs.  Ambiguity is a problem.  What happens when the analyst interprets system suitability requirements differently from the reviewer?  If it is unclear, does this spark a deviation?  What are the consequences of the way the method is worded?

 

Reagent List

Let the user know what the acceptable grades are, or at least the grades you used when developing the method.  This is useful information.

 

Materials

Does this method only work on a Waters instrument?  Have you only tried it on an Agilent HPLC?  I have seen this before, a method only works properly on one brand of instrument.  This section will resolve itself at method transfer to the QC lab.  If it doesn’t work on their HPLC, you won’t be able to transfer the method.

Give a part number for your column to make purchasing easier.

 

Reagent Preparation Volumes

Many times a method is written in terms of specific volumes.  For example: prepare 1 L of mobile phase.  But, what happens when QC needs 2 L of mobile phase in order to run the number of samples?  Some QC labs are flexible enough to handle this change, but others are not.  A statement should always be added to address flexibility, such as: Different volumes may be prepared as long as the overall volumetric ratios remain the same.

Degassing: for an HPLC method, it is probably safe to assume that all users will have a somewhat modern HPLC with degasser.  No need to require degassing.  If you must include it in your method, keep it flexible: Degas as necessary.

 

Standard Preparation Volumes

The same concept holds true for the standard preparation instructions.  If the method specifies 40 mg reference standard weighed into a 200 mL volumetric flask, could it also be appropriate to weight 20 mg standard into a 100 mL volumetric flask?  There are many times when a change of prepared volume is appropriate.  Add flexibility to your method here too: Different volumes may be prepared as long as the overall concentration remains the same.

For the standard preparation, you may argue that a specific balance shouldn’t be used to prepare a smaller weight.  However, that is the realm of the Laboratory SOPs and not an issue for an analytical method to address.  The method preparation assumes that the user knows which balance is appropriate for their use.

It is very helpful to write standard weight as a range for an easy to read guide of the required weight: 30 mg ± 2 mg.

Also helpful are solution stability ranges for all standard preparations: stocks, LOQ injections, resolution standards, and working standards.  A matter of adding a few injections to the solution stability portion of your method validation will provide much needed information to the HPLC method user.

 

Note: if you’d like to be a great analytical chemist, read everything that John Dolan writes.  He is the “LC troubleshooting editor” at LCGC Magazine.

http://www.chromatographyonline.com/Dolan

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