Analytical Method Authoring: Ensure that your Method is User Friendly for Quality Control- Part 3
In parts 1 & 2 of this blog post, I wrote about ways to make sure that the HPLC analytical method that you are developing is user friendly for the QC laboratory that will be performing the drug substance or drug product release. I am focusing on methods required for release of Phase 1 or Phase 2 clinical trial materials. Many of these items are also helpful for non-QC labs that receive the method.
I have discussed Materials & Reagents, Preparation of Mobile Phase, Diluents, Standard Preparation, Sample Preparation, HPLC Conditions, and Injection sequence.
Here, I continue with the last sections of a method: System Suitability, Calculations, Reporting, and Example Chromatograms.
Think hard about how System Suitability is handled. Are you including onerous calculations that aren’t justified? QC labs are high throughput. Any time that can be shaved from an analysis is helpful.
Take for example a standard check analysis: Do you need more than one injection of check standard? If precision has passed with standard 1, you may not need more than one injection of the check standard.
Make sure that your method is specific with regards to these calculations.
To which injections of Standard should Check Standard be compared?
Which injections of Standard should be used to determine compound retention time? Will it be the average of the precision injections, all Standards, one of the Standard injections?
Which injections should be used for determining Tailing, Resolution, etc.?
Sometimes, it is helpful to include “typical” values for various system suitability parameters. That way, column health can be tracked and provide early warning signs of column degradation.
Assay and Purity Calculations
Show the equations and include a thorough key. Make sure to specify units!
Be specific and detail how many decimal places should be reported.
Detail how to handle peaks near LOQ. Are peaks below the area of the LOQ injection not integrated? Or should they be quantified and then not reported if under the reporting limit?
Make sure the scale and quality of the chromatograms are useful to the end user. Include zoomed in chromatograms. Label peaks in order to simplify peak identification.
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.