Determination of titanium dioxide nanoparticles in milk samples by single particle ICP-QQQ

Importance of the topic

Titanium dioxide (TiO2) is widely used as food additive E171 for whitening and brightening. Although most particles are microscale, regulatory bodies require knowledge of any nanosized fraction due to potential health risks. Single particle ICP-MS enables simultaneous measurement of nanoparticle size distribution and number concentration, supporting compliance with EU nanomaterial definitions.

Objectives and study overview

The study aimed to demonstrate the capability of a triple quadrupole ICP-MS in MS/MS mode with O2/H2 reaction gases to quantify and size TiO2 nanoparticles in milk. Particular focus was on overcoming matrix interferences from calcium, sulfur and phosphorus common in dairy samples.

Methodology

Sample preparation involved dispersing TiO2 NP standards in water, probe sonication, and diluting into skimmed milk. Spiked milk samples were 100× diluted before analysis. Transport efficiency was determined using 30 nm AuNPs, and response factors were calibrated with ionic Au and Ti standards. Particle size calculations assumed spherical shape and known density of anatase TiO2.

Used Instrumentation

• Agilent 8900 ICP-QQQ with advanced MS/MS configuration
• SPS 4 autosampler
• Concentric MicroMist nebulizer and Scott double-pass spray chamber
• Quartz torch (1.0 mm i.d.)
• Reaction gas mode: O2/H2
• MassHunter Nanoparticle Application Module

Main results and discussion

Without reaction gas, measurement of 48Ti in milk was dominated by Ca-related and polyatomic interferences, preventing detection of particles below ~105 nm. Using O2/H2 in MS/MS mode shifted 48Ti to 48Ti16O+, efficiently removing interferences. This enabled reliable detection of nanoparticles down to ~36 nm. Size distributions in milk closely matched those in ultrapure water, with median diameters around 220–226 nm. Background levels were reduced, and sensitivity improved by using the most abundant Ti isotope.

Benefits and practical applications

The approach offers:

• Lower particle size detection limits by exploiting MS/MS interference removal
• High sensitivity and fast data acquisition with short dwell times
• Accurate size and concentration measurements for regulatory and QA/QC purposes
• User-friendly software for streamlined data processing

Future trends and applications

Research is expected to expand into other complex food matrices, explore alternative reaction gases, and integrate sp-ICP-QQQ with separation techniques for enhanced specificity. Development of certified nanoparticle reference materials and standardized protocols will further support industry and regulatory monitoring.

Conclusion

MS/MS operation of triple quadrupole ICP-MS with O2/H2 reaction gas provides a robust solution for characterizing TiO2 nanoparticles in milk. It overcomes major matrix interferences, lowers detection limits, and delivers reproducible size and concentration data essential for compliance and safety assessment.

References

• Larios R, Vidmar J, Hässmann L, Löschner K. Determination of titanium dioxide nanoparticles in milk samples by single particle ICP-QQQ. International Food & Environmental Analysis Summit, Toledo, Spain, 3–4 April 2019.
• ISO/TS 19590:2017 Nanotechnologies — Use of single particle ICP-MS to characterize nanoparticles.
• JRCNM 10200a. Titanium dioxide nanoparticle reference material, anatase, nominal primary size 115 nm.