I suggest starting your trials by considering Acetonitrile (70:30, v/v) as primary choice. Acetonitrile often provides better resolution and peak shape. It also has lower viscosity, which can reduce backpressure in the HPLC system. You can alter the compositions 80:20, 60:40, v/v. However, next choice is methanol as it provides adequate solubility and separation of mirtazapine powder.

2d ago

Rajshekher Upadhyay,

If you don't want to use buffer then go for Water and organic solvent mixture adjust pH with Ortho Phosphoric Acid (OPA) or Tetrahydrofuran(THF) depend upon your molecule pKa value.

Try using ACN, MeOH, Water with pH modifires like TFA, Formic acid, OPA, Ammonia, Acetic acid (all HPLC/LCMS Grade). pH modifires conc. starting from 0.05 % either in single or both mobile phases. Also, make sure which column you are using, Normal or Reverse C18.