Analytical Method Authoring: Ensure that your Method is User Friendly for Quality Control- Part 2
In part 1 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.
Last time, I discussed Materials & Reagents, Preparation of Mobile Phase, Diluents, etc., and Standard Preparation.
Here, I continue with further sections Sample Preparation, HPLC Conditions, and Injection sequence.
Sample Preparation- API
The flexibility/clarity for this section is similar to that for standard preparation. If possible, allow for the preparation of different volumes of sample with a statement such as: Different volumes may be prepared as long as the overall concentration remains the same. In those rare instances where the volume of preparation needs to be kept exactly the same, note that fact for the analyst.
I have rarely seen this written into a method, however handling tips for extremely difficult drug substances would be very helpful. Some examples of API descriptors are: sticky, fluffy, static prone, etc.
Sample Preparation- Drug Product
There usually isn’t as much flexibility that can be written into a drug product section, unless you are working with solutions.
Note, though, if you require odd sized glassware or unusual equipment for the drug product method, warn the QC lab early so that they can prepare.
Does the column need longer conditioning than average, a longer wash than normal? Is the method prone to carryover? Consider adding a note to this effect.
Build some flexibility into the appropriate sections of the injection sequence section. Specify that the stated injection sequence is a recommendation. Or provide injection number ranges for the more flexible injections such as diluent and primer.
Without this flexibility, the QC lab may be locked into running a certain number of injections when not necessary. For example, the method calls for three diluent injections at the beginning of a run, and the QC analyst runs 4 diluent injections, is that a deviation?
Of course, the required injections should be specified exactly: six injections of Standard 1, followed by one injection of Standard 2.
Up next time: System Suitability and Calculations
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.