Losartan Potassiun Tablets USP Monograph Test 1

[danor285]

Hi.
I am having some issues with the cromatographic system for Dissolution test
for Losartan Potassium Tablets.

Anybody has experience with this metohd?
I need to know the Retention time, Tailing, theoretical Plateau, height and width in order to compare with my results in differents brnads of HPLC (i'm having big differences y that parameters).

This is the chromatographic system:
Solution A: 0.1% v/v phosphoric acid in water
Mobile phase: Acetonitrile and Solution A (40:60)
Chromatographic system
(See Chromatography á621ñ, System Suitability.)
Mode: LC
Detector: UV 254 nm
Column: 4.0-mm × 25-cm; 5-μm packing L1
Column temperature: 35°
Flow rate: 1 mL/min
Injection volume: 20 μL
Run time: NLT 1.5 times the retention time of losartan

Thanks in advance

[DR]

As this is an isocratic method, the brand of LC used should have minimal impact on your retention time etc. (unless you have an unusually large volume between your injector and column or column and detector).
I suggest going through some of the column vendor websites and searching for Losartan. Many will probably have sample chromatograms using their L5 media for you to look at.

[vmu]

According to the USP Chromatographic Database, the Inertsil ODS-3 column from GL Sciences was used for the development of this method in this monograph.

[Consumer Products Guy]

Hi.
Injection volume: 20 μL

Wow - I NEVER used an injection volume that large, not in 36 years using HPLC. I've never used that specific monograph, but USP <621> permits certain modifications.

Most often we used 5μL or 3μL injection volumes.

And when I see a detector wavelength of 254nm, the first thing that triggers in my mind is that this must be a quite-old monograph, from the days where many detectors were not variable wavelength, and were 254nm only.

[vmu]

Hi.
Injection volume: 20 μL

Wow - I NEVER used an injection volume that large, not in 36 years using HPLC.

It's a typical injection volume for a 250 mm x 4.0 (or 4.6) mm column.

when I see a detector wavelength of 254nm

Actually, the WL is 256 nm in the monograph.
______________________________________
Analysis of Losartan Potassium (Inertsil ODS-3)
https://www.glsciences.com/viewfile/?p=LA937
This differs somewhat from the monograph: 60% ACN instead of 40% ACN, the latter leading to substantially higher retention time; 220 nm instead of 256 nm; 10 μL instead of 20 μL; 250 ppm in the sample instead of 25 to 100 ppm).

Analysis of Losartan Potassium (Inertsil ODS-4)
https://www.glsciences.com/viewfile/?p=LA939

[Mike H.]

We used to test losartan free base at Merck Flint river, before it was sent to another site to turn into K salt. Wavelength used was 220nm for the impurity profile.

Dissolution methods are really easy to develop so it's difficult to understand how it's causing issues.

If I was given losartan tablets for dissolution assay, I'd probably pick a EC-C18 agilent poroshell 50mm, 4.6mm column. Isocratic mode obviously with 0.1% H3PO4/ACN . Do a couple injections to get the RT under 5min through tweaking on MP% and you're set. If you're using a good LC ie. agilent system, you'll have no problems. good luck.

Edit: don't use a 250mm column for a dissolution method. As soon as I saw this, I figured it was developed by a contract lab. Run times are too long. 50mm column are the way to go.

[DR]

We used to test losartan free base at Merck Flint river, before it was sent to another site to turn into K salt. Wavelength used was 220nm for the impurity profile.

Dissolution methods are really easy to develop so it's difficult to understand how it's causing issues.

If I was given losartan tablets for dissolution assay, I'd probably pick a EC-C18 agilent poroshell 50mm, 4.6mm column. Isocratic mode obviously with 0.1% H3PO4/ACN . Do a couple injections to get the RT under 5min through tweaking on MP% and you're set. If you're using a good LC ie. agilent system, you'll have no problems. good luck.

Edit: don't use a 250mm column for a dissolution method. As soon as I saw this, I figured it was developed by a contract lab. Run times are too long. 50mm column are the way to go.

If they're running a monograph method, they have to stick to the monograph's rules regarding changes in column dimensions, flow rates, MP composition and injection volume.

A poroshell column (especially a short one) may not work at all given its limited capacity and the possibility of needing a fairly high amount of analyte (large injection volume) if it has a weak chromophore.
Inertsil ODS-3 is an excellent stationary phase, though you may be able to at least go with a shorter, narrower bore version and meet USP requirements once you've adjusted your flow rate and (maybe) injection volume.

RE: the ease of dissolution method development - It's usually not difficult to develop a chromatographic method to show a fairly narrow range of analyte concentration from dissolution samples, but making sure that a dissolution method is discriminating and appropriate for a given API can be a challenge, especially when encountering extremes of API solubility in aqueous media...

[Mike H.]

We used to test losartan free base at Merck Flint river, before it was sent to another site to turn into K salt. Wavelength used was 220nm for the impurity profile.

Dissolution methods are really easy to develop so it's difficult to understand how it's causing issues.

If I was given losartan tablets for dissolution assay, I'd probably pick a EC-C18 agilent poroshell 50mm, 4.6mm column. Isocratic mode obviously with 0.1% H3PO4/ACN . Do a couple injections to get the RT under 5min through tweaking on MP% and you're set. If you're using a good LC ie. agilent system, you'll have no problems. good luck.

Edit: don't use a 250mm column for a dissolution method. As soon as I saw this, I figured it was developed by a contract lab. Run times are too long. 50mm column are the way to go.

If they're running a monograph method, they have to stick to the monograph's rules regarding changes in column dimensions, flow rates, MP composition and injection volume.

A poroshell column (especially a short one) may not work at all given its limited capacity and the possibility of needing a fairly high amount of analyte (large injection volume) if it has a weak chromophore.
Inertsil ODS-3 is an excellent stationary phase, though you may be able to at least go with a shorter, narrower bore version and meet USP requirements once you've adjusted your flow rate and (maybe) injection volume.

RE: the ease of dissolution method development - It's usually not difficult to develop a chromatographic method to show a fairly narrow range of analyte concentration from dissolution samples, but making sure that a dissolution method is discriminating and appropriate for a given API can be a challenge, especially when encountering extremes of API solubility in aqueous media...

Trityl losartan has a good chromophore at 220nm. None of the cautions stated is an issue for this specific compound, except if poster is forced to use USP method. I'd find a new line of work if I was forced to use USP methods.
Good luck.