# Quantitative Transfer of Volatile Standards

(Edited w/ updates) Okay, long story short I work in a lab which has been working on cannabinoid analysis (in the licensed Canadian market) and have had a lot of issues surrounding the standards/response factors varying over time.

They are only available in pure methanol or ACN, are very expensive, and only come in $$\pu{1 mL}$$ quantities. I currently micropipette $$\pu{150 \mu L}$$ of these into a vial and then dilute, though the vapour pressure of the solvent causes it to immediately push droplets back out of the pipette tip, meaning the volume changes slightly based on the speed at which you transfer, and I think this (among other things, like slow evaporation of retained stocks in storage) is causing variation. Relative response factors between cannabinoids vary up to 30% between different preparations on different days, which is unacceptable.

So I need to both conserve the liquid I use and find a way of transferring that can reduce the effect of volatility. I proposed weighing the ampule, transferring quantitatively to volumetric flask and weighing again, then back calculating the mass amounts using density, as the concentrations come per volume. I was confused about what my manager's issue with the idea was at first but clarified and it was about potential effect of the dissolved cannabinoids on the density of the solution via partial molar volume effects on the manufacturer's end. Aka how much would this affect density and are the concentrations they gave us reliable? They're FDA exempt, meaning they're unregulated and there is no one "gold standard" preparation or test method.

I wrote a pseudo-proof for this effect being negligible (TL;DR because 2.5mg solute of any kind out of 786mg solvent would produce a variation of <0.5% in density even when wildly exaggerating the partial molar volume effects) and our chief scientific officer reviewed and signed off on it so I'm going to be doing the gravimetric transfer.

Ampoule chips were not really a concern, they very reliably break cleanly and any chips are likely too small to be seen/matter much on that same ~782mg scale during my preparation.

• What are you using the standard for? – Buck Thorn May 31 at 16:22
• If you're transferring the entire contents to a volumetric flask, you don't need to mess about with density. You will have the mass from the ampoule weighings. – Beerhunter May 31 at 21:48
• @Beerhunter: The ampule could be chipped and could loose some weights. – Mathew Mahindaratne Jun 1 at 7:02
• @Night Writer UPLC assay of cannabinoid content from a whole whack of different products. I'm responsible for developing methods to extract and test new dosage forms. Actually get something new in almost every week. – Donald Bowins Jun 1 at 18:03
• >though the vapour pressure of the solvent causes it to immediately push droplets back out of the pipette tip, || You can cool the pippette and the ampule in a freezer... – permeakra Jun 1 at 19:19