Dissolution problem Clidinium Br and Chlordiazepoxide HCL

[phammer]

I'm a new member to this site and thank you all for contributing to this great forum.

I have been trying to verify a dissolution method from the USP monograph for Chlordiazepoxide HCL and Clidinium Bromide capsules and I have not been sucessful at doing it, can you please help? The problem I'm running into is getting reproducibility of peak area for Clidinium.

I prepared 1 USP standard consisting of Clidinium bromide (0.0025mg/mL) and Chlordiazepoxide HCL (0.005mg/mL). I put the standard solution into 8 vials (no filtering) and make 2 injections of 100uL from each vial. The peak area for Chlordiazepoxide HCL is consistent at RSD <0.5%. The peak area for Clidinium bromide does not yield consistent result, sometimes I would get RSD=2.5%, 3.5%, 2.0%, 8.7%, etc. The Clidinium bromide peak does not show any tailing or degradation.

Does anyone have any suggestion? I'm certain that this is not an instrument issue, because if it is then the RSD for Chlordiazepoxide HCL would also be more than 2.0%.

I ran the same experiment on 3 different Perkin Elmer series 200 HPLC with UV detector and Diode Array Detector and I got the same result.

[Nour]

what is the signal-to-noise ratio of clinidium peak? lower ratio implies higher RSD

[tom jupille]

In addition to nour's suggestion, take a look at your detection wavelength relative to the absorbance spectrum. If you are working on a slope (as opposed to lambda(max), then small variations in wavelength can generate relatively large errors in the signal.