USP Tryethyl Citrate - Assay / Related chromatography issue

[dico]

Dear all,

I hope this message finds you well.

I would appreciate your support in resolving an issue I encountered during the verification of the USP Assay/Related Substances test for Triethyl Citrate.

Specifically, I am experiencing failures in the SST (System Suitability Test) — including standard check and %RSD — for the two components. The peak for Triethyl Citrate shows baseline interference, which is contributing to the SST failure.

A significant challenge is that, following the USP method, the standard concentration of 0.02 mg/mL in Empower produces an area response of 6-7, which is quite small and likely to cause SST failure due to insufficient peak area. Unfortunately, I cannot modify any parameters of the method.

I would like to ask if anyone has experience with testing this excipient and could suggest any improvements or adjustments I might consider to address this issue.

Thank you in advance for your assistance.

Best regards,
Simone

[DR]

Lots of Empower users with Agilent GCs make processing methods that include a multiplier for your detector's channel in your method set (I think that's where you put it) - typically something on the order of 1^5 so that you do not have to carry 10 decimal places to figure out your RSDs and such.

[dico]

Thnaks for this info , however i cannot change this setting.

Are there , other paramters of the gc method that i can i change to have a better signal or bigger area ( exepct of the injection volume or the split mode ) ?

[vmu]

There are many parameters, including the temperature program, you can change according to USP chapter <621> Chromatography. You can try another instrument and another column (of the same type). You can vary the air and hydrogen flow rates in FID. The signal-to-noise ratio (rather than the absolute signal) is the parameter you should be interested in. The lowest impurity limit in the monograph for triethyl citrate is 0.2 % corresponding to 0.02 mg/mL; therefore, the S/N must be NLT 10 at 0.02 mg/mL. The higher S/N is better.

[vmu]

It is interesting that in the USP monograph for triethyl citrate, the system suitability for impurities is poorly written. RSD NMT 3.0 % for the triethyl citrate peak with 0.02 mg/mL solution is required there, but the particular quantity for which RSD should be calculated is not clearly specified. It may be interpreted as RSD of peak area, peak height, retention time...

In the assay part of the same monograph, the authors clearly require RSD NMT 1.0 % for the peak area ratio Area Standard / Area Internal standard, with concentrations of 1 mg/mL for both compounds.

[Consumer Products Guy]

It is interesting that in the USP monograph for triethyl citrate, the system suitability for impurities is poorly written.

I found many USP Monographs to be poorly written, vague, and confusing....