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Significance of the Topic


The demand for uncompromised UHPLC systems that combine ultra-high speed, high resolution, robust pressure control, minimal carryover and versatile expandability has grown across pharmaceutical, environmental, food, and clinical laboratories. Shimadzu’s Nexera system was designed to meet these requirements without sacrificing reliability or performance.

Objectives and Study Overview


This work presents the evolution of the world’s only “no compromise” UHPLC platform, originally launched in 2010 and recently upgraded with a low-pressure gradient function and extended flow range up to 10 mL/min. The goal was to develop a truly all-round HPLC capable of high throughput, superior reproducibility, and broad application flexibility.

Methodology

  • System pressure range up to 130 MPa (19 000 psi) with micro-plunger precision pump control and ultra-low volume mixer (20 µL).
  • Fast autosampler injection (10 s) with loop-injection option, multi-solvent internal and external rinse functions, and auto-pretreatment for internal standard addition.
  • Precise column temperature control up to 150 °C via Intelligent Heat Balancer and solvent pre-heater, supporting high-temperature and green LC.
  • Flexible quaternary low-pressure gradient unit for dynamic blending of four solvents in a single pump.

Used Instrumentation

  • Shimadzu Nexera UHPLC with LC-30AD pump and low-pressure gradient unit
  • SIL-30AC autosampler with overlapping injection and multi-rinse capability
  • CTO-30A column oven and Rack Changer II sample cooler (4–40 °C)
  • Detectors: SPD-20A/M20A UV/photodiode array, RF-20Axs fluorescence
  • Shimadzu LCMS-2020 single quadrupole mass spectrometer
  • Shim-pack XR-ODS III UHPLC columns (1.6 µm & 2.2 µm particles)

Main Results and Discussion

  • Ultra-fast analyses: 25× speed increase using sub-2 µm columns and higher flow rates; 14× speed with 2.1 × 100 mm, 1.8 µm at elevated temperature.
  • High resolution: 5-fold gain in theoretical plates with longer sub-2 µm columns at comparable analysis times.
  • Carryover reduction: <0.0004% for caffeine, undetectable levels for chlorhexidine and amines via combined rinse functions.
  • Injection precision: ≤0.3% RSD for internal standard peak ratios (0.2–40 µg/mL) and reproducible volumes down to 0.1 µL.
  • Gradient accuracy: six-fold finer resolution (0.1 s step) and efficient mixing enable reliable ultra-fast gradients.
  • LC-MS front-end performance: 15 000 u/s scan, 15 ms polarity switching, detection of 30 pharmaceuticals in a 30 s run.

Benefits and Practical Applications

  • High-throughput screening and QA/QC workflows with minimal downtime.
  • Bioanalytical LC-MS applications requiring near-zero carryover.
  • Green chromatography using water-only mobile phases at elevated temperatures.
  • Advanced method development via four-solvent gradients and multi-mix configurations.
  • Multidimensional LC and online SPE integration due to modular design.

Future Trends and Potential Uses


Continued integration with advanced mass spectrometry (ion mobility, improved ion sources), further automation of sample pretreatment, and expansion into multidimensional LC and green analytical workflows will drive next-generation laboratory productivity.

Conclusion


Shimadzu’s Nexera UHPLC platform delivers uncompromised speed, resolution, robustness and expandability. Through innovations in pump design, mixing technology, rapid injection and multi-rinse autosampling, Nexera meets diverse analytical demands without trade-offs.

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