Conclusion
A major step in qualification is creating a clear list of critical items and understanding dependencies among those items. LC/MS systems are highly sophisticated and tightly coupled: small physical effects (leaks, dead volume, injector behavior, gradient timing) can dominate performance, especially under fast separations.
Modern fast LC with narrow-bore columns reduces tolerances: dead volume and fittings matter more than conventional configurations described in older textbooks. Designers should therefore perform calculations directly from chromatography theory for the intended geometry and operating regime.