Why is acetonitrile preferred over methanol in HPLC mobile phases?

Why is acetonitrile preferred over methanol in HPLC mobile phases?
Acetonitrile holds distinct advantages over methanol in reversed-phase HPLC. Its UV cutoff is 190 nm versus methanol's 210 nm, enabling reliable detection at low wavelengths with flatter baselines and better quantitation. Acetonitrile also has lower viscosity, reducing system backpressure and allowing faster flow rates, which suits modern high-speed analysis. Methanol-water mixtures become notably more viscous, increasing pressure demands. In terms of elution strength, acetonitrile (3.12) is stronger than methanol (2.64), so less organic solvent is needed for equivalent retention. Selectivity also differs: acetonitrile acts as a weak proton acceptor, while methanol is both donor and acceptor, leading to different elution orders for compounds with hydrogen-bonding groups. These properties make acetonitrile the default choice for many gradient methods, especially in pharmaceutical and clinical testing applications.