After trying several solvents and mixes of solvents, I have always obtained about 94% recovery of Cinitapride (quantitation by HPLC) from tablets having a 170 mg average weight and Ludipress, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate and talc, as excipients. The HPLC method works well. Does anyone know what causes this phenomenon and if a method exists in order to increase recovery to at least 98%?

Many thanks.

Jorge.

Are you taking into account that your standard may not be 100% pure.

Anon II,

If that was the case shouldn't he/she see recoveries of higher than 100%?

Anon III -

You're right, sorry for my brain lapse.

Anon II

Always 94%? Hmmm... Any systematic error possible? If you dissolve the pill in a fixed volume of solvent, you end up with a volume that is larger than the solvent volume. If you now inject 10 microliters of this stuff, you will get a lower value than if you inject 10 microliters of a standard...

Maybe there is simply 94% in there. Sometimes we don't trust ourselves when numbers aren't what we want. Is there a salt conversion factor being missed? Are you using pk hts with different diluent for std and sample? When the method was validated, did the recoveries come out at 100%?
It sound like you are getting complete extraction if several solvent systems give 94%. Let us know how this works out.

I have some questions:

I assume that you must filtrate your samples, are you throwing away the first ml? Do you have filtrate you standard and measured this area?
Have you tried to sonicate/heating your sample?
Have you tried to use the used cinitapride as standard?
Have you tried to use a whole tablet, desintegrate in 5 ml water, and diltute with solvent/mobile phase?

First of all, thanks to everybody for dealing with this matter.
In order to avoid differences related to the purity of the standard, I have used the same drug used as ingredient of the tablets as standard. Regarding the extraction of cinitapride from the tablets, the procedure is as follows: whole tablets are placed in a 50 ml volumetric flask, and the solvent is added to volume. It is sonicated for 15 minutes, enough time for the tablets to disintegrate completely (the same procedure is applied to reference and sample).
Then, the final volume in the flask is checked and adjusted.
In one of the assays the sample was heated (75°) before sonicating and shaking.
The injection volume is 20 µl of the filtrated solution . The recovery continues to be about 94 %.
Thanks,
Jorge

What is the content of your standard?

Have you tried a spiked blank recovery where you make a "tablet" containing everything except the active ingredient then add the proper amount of your standard active to the blank and follow through the extraction process? A poor spiked blank recovery would tend to indicate a problem in the method. If the spiked blank recovery is good, you might want to take a closer look at the samples you are testing.