Fast and accurate determination of K, Ca, and Mg in human serum by sector field ICP-MS

Electrolytes in serum are important biomarkers for skeletal and cellular health. The levels of electrolytes are monitored by measuring the Ca, Mg, K, and Na in blood serum. Many reference methods have been developed for the determination of Ca, Mg, and K in clinical measurements; however, isotope dilution thermal ionization mass spectrometry (ID-TIMS) has traditionally been the primary reference method serving as an anchor for traceability and accuracy to these secondary reference methods. The sample matrix must be separated before ID-TIMS measurements, which is a slow and tedious process that hindered the adoption of the technique in routine clinical measurements. We have developed a fast and accurate method for the determination of Ca, Mg, and K in serum by taking advantage of the higher mass resolution capability of the modern sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). Each serum sample was spiked with a mixture containing enriched ⁴⁴Ca, ²⁶Mg, and ⁴¹K, and the ⁴²Ca⁺:⁴⁴Ca⁺, ²⁴Mg⁺:²⁶Mg⁺, and ³⁹K⁺:⁴¹K⁺ ratios were measured. The Ca and Mg ratios were measured in medium resolution mode (m/Δm?≈?4 500), and the K ratio in high resolution mode (m/Δm?≈?10 000). Residual ⁴⁰Ar¹H⁺ interference was still observed but the deleterious effects of the interference were minimized by measuring the sample at K?>?100 ng g^?1. The interferences of Sr⁺⁺ at the two Ca isotopes were less than 0.25 % of the analyte signal, and they were corrected with the ⁸⁸Sr⁺ intensity by using the Sr⁺⁺:Sr⁺ ratio. The sample preparation involved only simple dilutions, and the measurement using this sample preparation approach is known as dilution-and-shoot (DNS). The DNS approach was validated with samples prepared via the traditional acid digestion approach followed by ID-SF-ICP-MS measurement. DNS and digested samples of SRM 956c were measured with ID-SF-ICP-MS for quality assurance, and the results (mean ± expanded uncertainty in mg dL^?1 unit) for Ca (DNS?=?10.14?±?0.13, digested?=?10.11?±?0.10), Mg (DNS?=?2.093?±?0.008, digested?=?2.098?±?0.007), and K (DNS?=?15.48?±?0.11, digested?=?15.50?±?0.28) were in good agreement with the certified values (Ca?=?10.17?±?0.06, Mg?=?2.084?±?0.023, K?=?15.55?±?0.13). Major sources of uncertainty are sample measurement, spike calibration, and instrument factor including mass discrimination of the spectrometer and the detector deadtime.