The fast and easy method development with latest generation UHPLC equipment has been demonstrated. Scouting of five different mobile phase combinations to find the best method condition was done without user interaction. Therefore, the eluent switching capabilities of the Vanquish Binary Pump H and Chromeleon 7.2 software support was applied for data evaluation. The highly efficient Accucore Vanquish C18+ column with 1.5 μm particles allowed method speed-up by a factor of two without compromising resolution. It was demonstrated that the Vanquish Split Sampler HT could reproducibly inject within the nanoliter range and without the need for hardware or software changes. Superior calibration curves were generated by applying the wide injection volume range of the Vanquish Split Sampler HT.