Achieving Solvent Reduction and Lower Running Costs with Nexera X4

Solvent Reduction in HPLC Using Nexera X4 and 1-mm-ID Columns

Importance of the topic

Reducing solvent consumption in liquid chromatography addresses both environmental sustainability and laboratory operating costs. Organic mobile phases are a major recurring expense and a significant source of chemical waste in analytical labs. Downscaling chromatographic methods by adopting narrow-bore columns (e.g., 1.0 mm inner diameter) can substantially lower solvent usage provided instrument design preserves chromatographic performance. Demonstrating robust, low-dispersion operation with small-diameter columns is therefore important for widespread adoption of greener, lower-cost LC analyses.

Objectives and overview of the article

This application note reports a case study demonstrating solvent and cost reduction by combining the Nexera X4 liquid chromatograph with a 1.0 mm I.D. Shim-pack NovaCore C18-HB column. The goals were to:

• Quantify solvent savings when scaling column diameter from typical 3.0 mm and 2.1 mm formats down to 1.0 mm (at equal linear velocity),
• Confirm that Nexera X4’s low-dispersion flow path supports sharp peak shapes with narrow-bore columns, and
• Demonstrate practical chromatographic performance for a mixture of eight small-molecule pharmaceuticals.

Methodology

A mixed standard of eight small-molecule pharmaceuticals was used as the model sample. The principal experimental approach was to run gradient separations on a 50 mm × 1.0 mm, 1.7 µm Shim-pack NovaCore C18-HB column and compare solvent consumption and peak shapes to larger-bore columns and to a typical UHPLC system.
Key analytical parameters (summarized from the original table):

• Column: Shim-pack NovaCore C18-HB, 50 mm × 1.0 mm I.D., 1.7 µm
• Mobile phase: Pump A = 0.1% formic acid in water; Pump B = acetonitrile; gradient 5% B (0 min) → 70% B (3 min) → 5% B (3–8 min)
• Column temperature: 50 °C
• Flow rate: 0.10 mL/min (linear velocity maintained when comparing different IDs)
• Mixer: micro mixer; sample loop: 15 µL; injection volume: 0.3 µL
• Detection: UV at 254 nm (SPD-M40 X4, standard cell)
• Analytes: (A) Antipyrine, (B) Benzoic acid, (C) Salicylic acid, (D) Hydrocortisone, (E) Furosemide, (F) Naproxen, (G) Probenecid, (H) Diclofenac

Used instrumentation

The study used the Nexera X4 UHPLC system (Shimadzu) coupled with a Shim-pack NovaCore C18-HB 1.0 mm column and an SPD-M40 X4 UV detector. Nexera X4 is emphasized for its low-dispersion flow path and minimized internal volumes to preserve column performance when small-diameter columns and low flow rates are employed.

Main results and discussion

• Solvent savings: Maintaining constant linear velocity, moving from a 3.0 mm column to a 1.0 mm column resulted in approximately a 9-fold reduction in solvent consumption. Switching from a 2.1 mm column to a 1.0 mm column produced about a 4.5-fold reduction. These values were normalized to the 3.0 mm column’s consumption taken as 100%.
• Chromatographic performance: Chromatograms obtained with the Nexera X4 and the 1.0 mm column showed sharp, well-defined peaks for all eight analytes under the applied gradient and low-flow conditions. A comparison with a typical UHPLC system running the same column revealed that Nexera X4 produced significantly narrower peaks, indicating lower extra-column dispersion and better preservation of column efficiency.
• Operational considerations: Achieving reliable performance at very low flow rates (0.1 mL/min) and sub-microliter effective injection volumes requires minimized system void volumes and accurate, low-volume injection capability. Nexera X4’s design addresses these needs through a low-dispersion flow path and micro-mixing components.

Benefits and practical applications

• Cost reduction: Substantially lower mobile phase consumption directly reduces reagent costs and waste disposal expenses.
• Environmental impact: Lower solvent usage decreases hazardous waste volumes and the laboratory carbon footprint associated with solvent procurement, transport, and disposal.
• Method translation: Laboratories running large numbers of routine assays—pharmaceutical QC, formulation analysis, environmental screening—can downscale methods to narrow-bore columns to achieve throughput and sensitivity while saving solvent.
• Performance retention: With appropriate instrumentation design (low extra-column dispersion), chromatographic separation quality can be preserved despite the reduced column diameter and flow rate.

Future trends and application opportunities

• Broader adoption of narrow-bore and capillary LC formats as instrument designs evolve to minimize extra-column dispersion and deliver reliable low-flow performance.
• Integration with mass spectrometry: Lower flow rates are advantageous for direct coupling to electrospray MS, improving ionization efficiency and reducing solvent load on MS interfaces.
• Method standardization for green analytical chemistry: Development of validated workflows that prioritize solvent reduction without compromising regulatory requirements for QC/QA.
• Automation and high-throughput: Combining narrow-bore methods with automated sample handling can maintain or increase sample throughput while reducing per-sample solvent consumption.

Conclusion

Downscaling LC methods using 1.0 mm I.D. columns offers a straightforward route to major solvent and cost savings. Realizing these savings without loss of chromatographic performance depends on instrument design that controls extra-column dispersion and supports accurate low-volume injections. The Nexera X4 system demonstrated the ability to preserve sharp peak shapes and efficient separations at low flow rates, making narrow-bore approaches viable for routine analytical use with clear economic and environmental benefits.

Reference

Shimadzu Corporation. Nexera X4 application note: Achieving Solvent Reduction and Lower Running Costs with Nexera X4. First Edition, February 2026.