Analytical method for quantification of potassium citrate ?

[dhruvil81]

Hi all

This is Dhruvil Patel working with a R & D dept. of pharmaceutical company.

i m currently developing method for the oral solution containing Potassium citrate(1100 mg/ 5 ml) and Magnesium citrate (375 mg/ 5 ml). I could quantify magnesium citrate by complexometric titration( i.e. using EDTA) but i m facing problem in quantifying Potassium citrate.

Can anyone suggest me the related cleus regarding this problem or any analytical technique for the quantification of potassium citrate in presence of magnesium citrate ?

I have taken trials of ICP (Inductively coupled plasma) but i m getting lower results, assay comes out to be 70 % only. I have applied calibration curve technique for the analysis i.e by using linearity method. where linearity solutions were prepared from Potassium sulphate monohydrate over the concentration range of 2 -8 ppm.

Pls do the needful if someone had done this before.

Thanks

Regards
Dhruvil

[jimmyv]

I have done Citrate analysis by ion exclusion with 0.002 N Sulfuric acid as mobile Phase and a conductivity conductor. It will not differentiate between magnesium or potasium citrate. But if you have a value for magnesium citrate you could deduct that. Iused a Brownlee Polypore H 10 um ,25x7.0 mm column.

Jimmy

[HW Mueller]

One would think that one has K+, Mg++ and citrate in aqu. solution, maybe a little MgCitrate. Therefore it is surprising that ICP gives you wrong K+ values, what sort of sample introduction does the ICP use? Even a simple flame photometer with nebulizing sample introduction gave very reliable values for K+, when the system was kept clean (constant flow). Maybe your K2SO4 is not the monohydrate anymore?

[IC_Gal]

You might want to try an ion chromatography method to get K and Mg if you are having difficulties doing the analysis by ICP. There are some good cations columns out there that will allow you to analyze for them using an acidic mobile phase with conductivity detection. As was mentioned before citrate is often analyzed by ion exclusion but this won't tell you which is K and which is Mg.

[mohan_2008]

I dont buy Dhruvil's argument.

I did similar assays multiple times using ICP/OES (using Optical Emission Spectrometer) - K & Mg give pretty intense lines - that even at trace levels & when present with multiple elements- they can be quantified pretty accurately.

From the several ICP lines - use the lines meant for Mg++, K+ only. Make sure your sample is aspirated & nebulized properly.

[dhruvil81]

Dear Mohan,

First of all thanks for showing interest in the topic.
As i sad i have taken trials on the ICP. I am getting satisfactory results for Magnesium citrate, but i could not get the same in case of Potassium citrate.

I would like to know from u weather u did the same kind of fourmulation which i am doing ? If yes and if possible can u share the preparation procedure with me ? R u analysing both the elements at a same time or u r performing analysis using different runs ?

Pls send reply as soon as possible.

Once again Thanks
Regards

Dhrvuil

[mohan_2008]

Hi Dhruvil,

1. What kind of working concentration of Potassium are you aspirating.

2. Is it bracketed by your linearity working range. ICP has several orders of linear working range. However, for ions such as K+ - it is a better idea to bracket the working level.

3. What kind of solvent/digestion procedure is used for the sample prep.
I am trying to see, if an optimal solvent is used for digestion, with the citrate matrix.

4. Try some experiments with a known non-citrate matrix of Potassium. This is just to ensure it is not the citrate matrix that is causing this low recovery.

As per your question:

Yes, I did several formulations, solid, liquid, and gel formulations with atleast 10-15 elements in them; Pot & Mag in all of them, and always I used to get 100% recoveries.

One of the things I do: is keep my sample introduction chamber clean and tidy. Aspiration, Nebulizing ports & torch system cleaned on a weekly basis and performance tests done every Monday.

It is very critical to have the ICP in proper shape - otherwise it may lead to several false readings due to memory effects and improper atomization.

[dhruvil81]

Dear,
Tahnks a lot for replying so quickly.

Yes i am using the linearity method for the quantification. I have got my formulation that contains 1100 mg/ 5 ml of potassium citrate in it. It's wt. per ml is 1.37 . So it would be 58050 µg/gm of potassium in the sample solution.

I am working at 1 ppm target level. For this i m diluting 0.172 gm of sample into 100 ml with dilute HCl ( 0.1 N). Further 1 ml of this solution is diluted to 100 ml with the same diluent. I prepare linearity standard solutions of potassium ranging from 0.5 ppm - 1.5 ppm by diluting the stock solution prepared from K2SO4.H2O .

One more thing i wanted to share with u is i m also planning to prepare my sample by charring it. I ll take accurate weight of sample into Pt crucible, first i ll ignite it on to low terperature flame followed by heating it into the muffle furnace. Then i ll recover the inorganic material from crucible by dissolving it into diluted HCl. I hope this would remove entire sample matrices which might be interfering into the analysis.

I know there should not be any interferences in analysis by ICP, evenif i prepare sample in a manner i am doing it. but really don't know why the recovery is not coming.

Well i hope i would be able to solve the problem soon. But please do share your experience and knowledge in this regards. And also keep sharing your ideas.

Bye for now and take care.

Thanks

regards
Dhruvil

[mohan_2008]

Hi Dhruvil,

It is typical sometimes, the K+ ions may not have been extracted into your digestion solvent.

For your sample prep: Are you heating the sample in 0.1N HCl as part of the digestion process.

If not - try heating the sample in 50% volume of the digestion solvent and make it up to volume, after it gets to room temp.

Also, try these options:

1. Try 1N HNO3 - proceed with heating & digestion process as above.
2. Try Aqua Regia, and proceed with digestion (caution: use fume hood)

Try microwave extraction - if available.

Let me know, if any of this works.