Chromatography Forum

I need to do stability in solution for my rel subs standards and, after looking through both area and concentration calculations, was wondering which is best practice?

1. Measure area of the 6 Standards at Day 0. Weight adjust as appropriate. On Day 1,5,10 etc, prepare fresh standards, comply the original 6 samples and compare differences in area until you are over the spec.

2. Weigh out 6 sets of standards (assay these as samples), get the actual conc in mcg/ml and assay these with fresh complied standards. This is Day 0. Repeat for Day 1,5 etc with fresh standards and compare conc of original samples with Day 1 etc. Measure the difference as a % and stay in spec.

Are there any official guidelines on stability in solution studies? Thanks.

If you measure areas during different analysis occasions, you are including between day variations. This is especially dependant on some detector types.
I would recommend you to assay the solution for each day and calculate the difference on concentration basis.

There are no guidelines. But ICH Q2(r1) is not enough alone. I typically write a 'stability of solutions' section in my AMV protocols where I am evaluating concentrations of old solutions (HPLC mobile phase, reference standard, working sample) versus 'freshly made' standards.

Many companies have received a 'FDA 483 observation' because they have not demonstrated their solutions are stable. The period of evaluation is based on the time to fix an instrument (typically maximum of 5 days) so my evaluation is 1, 2, 3, 4, and 5 days. The acceptance criteria is based on the specification (example 98.0-102.0% label claim).

Thank you very much for the replies, I was told to use concentration as a Day 0 comparison as this is more accurate. Thanks.