Quantitative Analysis of Sweeteners in Beverages and Mouth Rinse Using Ligand Exchange Chromatography-MS with APCI Interface and Post-column Reagent Addition

Importance of the Topic

The accurate quantification of sugar alcohols and artificial sweeteners plays a critical role in food safety, regulatory compliance, and nutritional research. Rising consumer demand for low-calorie products and stringent labeling requirements drive the need for analytical techniques that deliver high sensitivity, selectivity, and throughput.

Goals and Study Overview

This study presents a novel liquid chromatography–mass spectrometry (LC-MS) approach combining ligand exchange chromatography with a single quadrupole mass spectrometer and atmospheric pressure chemical ionization (APCI). The method targets nine commonly used sugar alcohols and artificial sweeteners using pure water as the mobile phase and minimal post-column chloroform addition to enhance ionization efficiency.

Methodology and Used Instrumentation

• LC-MS system: Shimadzu LCMS-2020 single quadrupole with APCI interface
• Chromatographic column: Shim-pack SCR-101P ligand exchange column (7.9 × 300 mm)
• Mobile phase: Isocratic pure water at 0.60 mL/min
• Post-column addition: Methanol:chloroform (95:5) at 0.1 mL/min (final chloroform ~0.7%)
• Temperature settings: Column oven 80 °C; APCI interface 450 °C; DL 250 °C; block 200 °C
• Detection mode: Negative ion selected ion monitoring (SIM), monitoring [M+Cl]–, [M–K]–, or [M–H]– adducts as appropriate
• Calibration range: 0.04–500 mg/L with mixed standards in water

Main Results and Discussion

The ligand exchange column achieved baseline separation for most analytes, with three compound pairs resolved by distinct m/z values despite close retention times. Chloride adduct formation dominated ionization for sugar alcohols, while potassium and proton adducts were observed for acesulfame potassium and saccharin, respectively. Calibration curves exhibited excellent linearity (r2 > 0.999) across the full concentration range. Limits of detection ranged from 0.01 to 1 mg/L. Repeatability tests (n=6) showed relative standard deviations below 7% for most analytes, with maltitol and lactitol slightly higher but still within acceptable limits.

Benefits and Practical Applications

This method minimizes organic solvent use by employing water as the mobile phase and reducing chloroform concentration in the ionization stream. It delivers robust sensitivity and reproducibility suitable for routine quality control, research laboratories, and regulatory monitoring. The approach was successfully applied to sweetened soft drinks, probiotic beverages, and mouth rinse, yielding quantification results consistent with product labels.

Future Trends and Applications

Emerging trends include coupling ligand exchange chromatography with high-resolution mass spectrometry for enhanced specificity and metrology, development of fully water-based mobile phases to meet green analytical chemistry goals, integration with automated sample preparation workflows, and expansion to broader classes of glycosylated compounds. The technique has potential for on-site testing and high-throughput screening in food, pharmaceutical, and clinical settings.

Conclusion

A streamlined APCI-ligand exchange LC-MS method was developed for quantitative analysis of nine sugar alcohols and artificial sweeteners. By leveraging pure water chromatography and minimal post-column reagent, the method achieves sub-mg/L sensitivity, high reproducibility, and direct applicability to complex beverage and oral care matrices.

References

• Application News No. C74, Shimadzu.
• Kato Y. and Numajiri Y., Journal of Chromatography 562, 81–97 (1991).