Validation of Analytical Method for Determination of Thallium in Rodent Plasma and Tissues by Inductively Coupled Plasma–Mass Spectrometry (ICP-MS)

Abstract

Thallium (Tl) can be released as a byproduct of smelting, mining, and other industries, causing human exposure. There are knowledge gaps on the toxicity of thallium compounds, so the National Toxicology Program is investigating the toxicity of thallium (I) sulfate in rodents. We developed and validated a method to quantitate Tl in rodent plasma and secondary matrices. Primary matrix standards and validation samples were digested with nitric acid and analyzed for Tl by inductively-coupled plasma – mass spectrometry (ICP-MS). Method performance was validated for linearity, accuracy, precision, and other criteria. Calibration was linear from 1.25 to 500 ng Tl/mL plasma; accuracy (RE) was −5.9 to 2.6% for all calibration standards. The lower limit of quantitation (LLOQ) was 1.25 ng Tl/mL plasma, and the limit of detection was 0.0370 ng Tl/mL plasma. Intra- and interday RE and precision (RSD) were −5.6 to −1.7% and ≤0.8% (intraday) and −4.8 to −1.3% and ≤4.3% (interday), respectively, at three sample concentration levels. Standards up to 10.0 x 10³ ng/mL could be analyzed by dilution with digested blank matrix, with −6.4% RE and 5.4% RSD. Method was also evaluated in post-natal day 4 (PND4) Hsd:Sprague Dawley SD (HSD) dam and pup plasma, gestation day 18 (GD 18) HSD rat fetal homogenate, HSD rat urine, female HSD rat brain homogenate, female B6C3F1 mouse plasma. Background Tl was detected in control fetal and brain homogenates and urine at < 30% of LLOQ response. Results demonstrate that the method is suitable for determination of Tl in rodent matrices for toxicology studies.

Keywords:

• Environmental exposure
• inductively coupled plasma - mass spectrometry (ICP-MS)
• method validation
• rodent plasma and tissues
• thallium

Acknowledgements

The authors would like to thank Mr. Brad Collins and Dr. Pei-Li Yao for review of this manuscript.

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, Intramural Research project ZIA ES103316-04, and performed for the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract HHSN273201400022C (RTI, RTP, NC).