[RogueRose]

SO I wanted to verify the active ingredient in some OTC pills.  The active ingredient is an HCl salt at 120mg / pill. Other ingredients are vegetable cellulose and stearic acid.  The pills weight 300mg each

The active ingredient has a solubility of 80g/100ml H2O so for every ml of water I can dissolve 800mg and has a melting point of 230-255 I believe.  Stearic acid, at the temp I’m using, 20C has negligible solubility at .003g/L of water.  Microcrystalline cellulose is totally insoluble in water. 

The water I’m using was de-ionized then filtered 3x with a very high efficiency activated charcoal filter.  It was then cooked under 2ATM of pressure and distilled from thee leaving pure water. 


I took 30 pills and smashed them in a mortar and pestel and emptied powder into a beaker.  I added 20ml of water to the beaker and 10ml to mortar to get any remnants and dipped pestel in it.  Poured liquid in beaker. 

Mixture was stirred for 1-2 minutes every hour for 8 hours (covered while not in use) and then allowed to sit another 12 hours over night.  Again the mixture was stirred for 2-3 minutes the following day and then poured through a VERY fine SS mesh screen (IDK measurements that small) and into a .45 micron vacuum filtration receiving unit.  -8psi was pulled and liquid filtered quickly

A small glass evaporation dish was prepared and weighed  *completely* dry and weight was noted.  The filtrate was added and dish was set aside for the moment. 

I then rinsed the filter receiver unit and SS mesh with 15ml of water and collected in a bowl.  I stirred 2-3 times an hour for 4 hours before filtering this and adding to the previous sample.

I placed the evaporation dish in container with a generous amount of anhydrous CaCl2 (about 1lb)  and sealed it.  After a week it was apparent it was TOTALLY dry and some nice crystals had formed yet their seemed less than expected but I figured they were dense or the bottom layer was coated solid. 

The scale showed a final weight  minus dry dish weight at 1.13g!  That is about a 31-32 % yield, (scale reads to hundredths of gram). 

I repeated this experiment with a larger sample size *100 pills, and got about 29.5% yield. 

Has anyone noticed whether I have a procedure wrong or not doing something?  I’ve done quantitative analysis before and most results were with 2-3% of what I expected and in some of those I had to do 3-4 stages of extractions with multiple solvents and evaporations and such.  Here it is super simple straight forward. 

Can anyone see any errors?

[Borek]

Unlikely cause, but what is the volatility of the substance?

[RogueRose]

Unlikely cause, but what is the volatility of the substance?

Degrades at 381F from what I read.  but I never got over 100F and I didn't see oxidation or sublimation as being a possible issue. 

I forgot to add I washed the filter w/ 3-4ml distilled H20 after adding the second washing.

My conclusion is that there must be either something not right (dosing)with the pills or  the active ingredient is different

[Arkcon]

Briefly, no you're not doing it correctly.  I mean to say, you appear to be trying to perform a USP content uniformity assay, but I've never read of one done by quantitative massing, as you have here.   There are simply too many places in your procedure where there can be loss.  Briefly, USP standards, often mixed with a placebo is dissolved in a fixed volume, then tablets are separately dissolved in the same volume, and portions of the solution are subjected to a validated assay -- HPLC, GC, or UV absorbance.