Reduction of resolution between two chemical entity

[prashant.pqa]

Dear All
Nice to see all of you on this forum. I want some experts views for reduction of the resolution bewtween two drug molecules.
I am using mobile phase Phosphate buffer 25 mM pH7.0 with 0.1% Triethylamine:Acetonitrile(52:48%v/v) with C18 (250 X 4.6 5 micron) column. The flow rate is 1.0ml/min with column tempe.25C.
As i am developing the simultaneous method for two drugs. One drug molecule is eluting at 5.0 min and another is at 18.6min. There is difference of around 13.0 min between theses two drugs.
Can any one suggest how i can reduce this 13min difference between these two molecule and also my aim first drug should come elute more than 6.0 min.
Also the total run time of system should not exceed more than 20min.

If i will use the Acetonitrile methanol mixture is it will be useful ?
Kidly give your valubale suggestion.

Thank you in advanced.

[AA]

1:Increase organic or
2:Use a gradient or
3:use a shorter column or
4:Increase the flow rate or
5:Incease the temperature or

[Consumer Products Guy]

2: use gradient

1,3,4,5 will also make the first component elute sooner, so you need to be careful that it still is retained sufficiently. Better consult a book to learn how to set up a gradient, and sufficient reequilibration time; if you already knew how to do that, you likely wouldn't have had to ask your question.

[mbicking]

You have a very large resolution number. If there are no other peaks in the chromatogram between the two peaks of interest, then you can use a much shorter column.

If you also choose a shorter column with smaller particles (4.6 X 75 mm, 3 um), you can operate at a faster flow and your retention times will be even smaller. Resolution should be acceptable.

Why do you want your first peak to elute after 6 minutes? You want this peak to be away from the void volume, but 6 minutes is too long, unless you have interferences that elute early.

[AdrianF]

What is the nature of the drugs - basic acid etc.