i am trying to develop hplc method of analysis for sibutramine hcl

i have used 35:65(buffer;acn) system my ph of the m.p is 6.0 but i am getting avery very broad and having a soch tailing that is around3 to 4 so can yousugget onother method or possible changes to this method

What column are you using? Sibutramine has a pKa of about 8.5 so a mp with a pH 6.0 seems like a poor choice for reversed phase chromatography. Your tailing is probably due to secondary interactions with the stationary phase. That is your basic compound is interacting with acidic sites on the stationary phase causing tailing. You can try the following:

1) Reduce the pH of the mobile phase to around 2 and see if you can protonate the acidic sites and reduce tailing.

2) You can also add a basic mobile phase modifier to compete with sibutramine for the acidic sites. Try TEA (triethylamine).

3) Try a column with high purity silica - low metal content reduces the acidity of the silica.

4) Try a base stable column like the Xterra from Waters or Devolsil from Nomura with a basic mobile phase and deprotonate sibutamine this will probably also greatly increase retention.

5) Try a column with an imbedded amine group.

Also, make sure that what you are seeing is tailing and not column overload. I have seen some basic drugs overload a column at very low on column amounts. This can occur when the charged (protonated) form of your drug is poorly soluble in the adsorbed ACN layer on your column. If your peak looks like a right triangle and its retention time increases when you inject less it is probably overloaded. If there are no sample stability issues I would probably start with 4. Good Luck.

thanks for your suggestions i treid with
bondapak c 18 column and added a 5 ml of tea to buffer and lower down the ph to 6 i have got the very sharp peak at rt of 9.2 i have done linearity and reproducibily on this system it was ok so i think that my probleam is solved now have any more suggestion on this.