National Institute of Standards and Technology, 100 Bureau Dr. Stop 8391, Gaithersburg, MD, 20899-8391, USA,
Anal Bioanal Chem. 2013 Nov;405(27):8761-8. doi: 10.1007/s00216-013-7320-4. Epub 2013 Sep 1.
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 (44)Ca, (26)Mg, and (41)K, and the (42)Ca(+):(44)Ca(+), (24)Mg(+):(26)Mg(+), and (39)K(+):(41)K(+) 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 (40)Ar(1)H(+) 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 (88)Sr(+) 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.
血清中的电解质是骨骼和细胞健康的重要生物标志物。通过测量血液中的 Ca、Mg、K 和 Na 来监测电解质的水平。已经开发出许多用于临床测量中 Ca、Mg 和 K 测定的参考方法；然而，同位素稀释热电离质谱法（ID-TIMS）传统上一直是主要的参考方法，为这些二级参考方法的溯源性和准确性提供了依据。在进行 ID-TIMS 测量之前，必须分离样品基质，这是一个缓慢而繁琐的过程，阻碍了该技术在常规临床测量中的应用。我们已经利用现代扇形场电感耦合等离子体质谱（SF-ICP-MS）更高的质量分辨率能力，开发了一种快速准确的血清中 Ca、Mg 和 K 测定方法。每个血清样本都用含有浓缩（44）Ca、（26）Mg 和（41）K 的混合物进行了加标，测量了（42）Ca(+):(44)Ca(+)、（24）Mg(+):(26)Mg(+) 和（39）K(+):(41)K(+) 比值。Ca 和 Mg 比值在中分辨率模式（m/Δm ≈ 4 500）下测量，K 比值在高分辨率模式（m/Δm ≈ 10 000）下测量。尽管仍观察到残留的（40）Ar(1)H(+)干扰，但通过在 K > 100 ng g(-1) 下测量样品，将干扰的有害影响降至最低。两个 Ca 同位素上 Sr(++) 的干扰小于分析物信号的 0.25%，并用 Sr(++):Sr(+) 比值通过测量 Sr(+) 强度进行校正。样品制备仅涉及简单的稀释，这种使用简单稀释的测量方法称为稀释和喷射（DNS）。DNS 方法通过传统的酸消解方法制备的样品进行了验证，随后进行了 ID-SF-ICP-MS 测量。使用 ID-SF-ICP-MS 测量了 SRM 956c 的 DNS 和消解样品，以进行质量保证，并对 Ca（DNS = 10.14 ± 0.13，消解 = 10.11 ± 0.10）、Mg（DNS = 2.093 ± 0.008，消解 = 2.098 ± 0.007）和 K（DNS = 15.48 ± 0.11，消解 = 15.50 ± 0.28）的结果（以 mg dL(-1) 单位表示的平均值 ± 扩展不确定度）与认证值吻合良好（Ca = 10.17 ± 0.06，Mg = 2.084 ± 0.023，K = 15.55 ± 0.13）。不确定度的主要来源是样品测量、加标校准和仪器因子，包括光谱仪的质量歧视和探测器死时间。
