Accuracy and Reliability in Trace Element Analysis

APPLICATION NOTE

AUTHOR Joerg Michel, Ph.D.

PerkinElmer

Rodgau, Germany

ICP - Mass Spectrometry

Introduction

Inductively coupled plasma mass spectrometry (ICP-MS) has become the go-to technique for the trace analysis of elements such as nickel (Ni), arsenic (As), mercury (Hg) and copper (Cu) found in bodily fluids. Through this method, individual elements or panels of elements comprising both toxic and essential elements are analyzed, offering doctors invaluable insights into their patients' health conditions. Researchers have uncovered correlations between essential element levels and a range of health issues, including metabolic dysfunctions, environmental impacts, and dietary patterns. Moreover, with the increasing prevalence of orthopedic implants, elements like titanium (Ti) and cobalt (Co) have also become commonly analyzed analytes. While these elements are not categorized as essential or toxic, their analysis offers medical practitioners vital information concerning implant deterioration.

Blood and serum present a common hurdle in trace-elemental analysis within biological matrices. Blood is a complex blend primarily comprising of water-containing proteins, glucose, mineral salts, hormones, and both red and white blood cells. Serum is derived from blood and has a comparable composition but lacks red and white blood cells as well as fibrinogens.

The NexION® 5000 multi-quadrupole ICP-MS is the ideal solution for this application. It features two full-resolution analyzer quadrupoles, in conjunction with Universal Cell Technology (UCT) to eliminate spectral interferences, using Collision and Reaction cell modes. The main advantage of the multi-quadrupole feature is the ability to select the mass of interest using the first transmission analyzer quadrupole (Q1), rejecting all other masses, in conjunction with the Universal Cell (Q2) that can eliminate on-mass interferences or react the analyte of interest with a gas to mass shift it to a higher mass, free of interferences, unleashing MS/MS or Mass Shift scan modes of operation.

Elemental Analysis of Serum Using the NexION 5000 ICP-MS

Another important advantage of the proprietary multi-quadrupole technology incorporated in the NexION 5000 ICP-MS is the secondgeneration Triple Cone Interface with OmniRing™ technology, that significantly improves sensitivity, which minimizes peak tailing/fronting from neighboring masses, making it possible to measure an element within 1 amu of a high-concentration element. 

This design facilitates interference-free measurement of the analytes of interest. Plus, combined with the proprietary Extended Dynamic Range (EDR) capabilities of the UCT, both trace and nutrient concentrations of the required analytes can be measured in a single analytical run.

In this work, we demonstrate that by employing a simple dilution of the serum samples with a suitable diluent, it is possible to measure panels or individual analytes quickly and accurately using the NexION 5000 ICP-MS, without upstream digestion of the samples.

Experimental

The method described here is based on the use of commercial calibrators with known target values and simple sample dilution.

Serum samples can be diluted with either a slightly acidic or a basic solution. However, if it is necessary to determine iodine in the serum, a basic diluent needs to be used, as a slightly acidic sample preparation (0.1% HNO3) can cause iodate and iodide to gradually react to form iodine and water.

The successful analysis of biological matrices using ICP-MS involves not only maintaining a clean laboratory environment and proper sample preparation to minimize contamination, but also requires the use of high-quality reagents and ultra-pure-grade standards. To ensure analytical accuracy and validate the method, it is necessary to use certified reference materials (CRMs). 

In order to eliminate the spectral interference on some isotopes that often occur in biological materials due to the high content of organics and salts, the NexION 5000 ICP-MS advantageously leverages the MS/MS and Mass Shift scan modes with the extremely powerful dynamic reaction cell (DRC) technology. The NexION 5000 thus allows for a straightforward and rapid analysis of this demanding biological matrix, serum.

Instrumental Parameters

All analyses were performed on the NexION 5000 ICP-MS in the configuration shown in Table 1. To increase sample throughput, ESI FAST (PerkinElmer) with PerkinElmer-ESI SC2/4 was used. The ESI FAST system encompasses a flow injection valve that loads the sample into a loop quickly and then injects it straight into the nebulizer, thus decreasing sample-to-sample times and carryover between samples. In this case, we used a 6-port valve as the IS is added into the diluent.

Standards and Sample Preparation

Serum Diluents

In the experiments described here, an acidic diluent was used. A diluent of 0.1% HNO3 and 10 μL each of a 1 g/L Rh and 1 g/L Re solution, as internal standards (IS; concentration = 10 μg/L), was prepared in a 1 L PTFE bottle with deionized water. If a basic diluent is preferred, a mixture of EDTA, isopropanol and ammonia can be used (see Appendix A for an example of a basic diluent). 

When working with the acidic diluent, the rinsing stations in the ICP-MS autosampler should also be rinsed with at least 0.1% HNO3, preferably with 2-5% HNO3. The carrier solution (carrier) when using a flow injection introduction system is also 0.1% HNO3 without internal standards (IS) (for instructions on basic diluents, (see Appendix A).

Preparation of Calibrator and Storage

A ClinCal® Serum Calibrator is used to calibrate the ICP-MS system. Reconstitute the ClinCal® serum with 3 mL of deionized water for approximately 30 min by using a roll-shaker or gently swirling. These reconstituted calibrators are to be prepared fresh daily and can last up to 8 hours at room temperature. The standards can be frozen at -18°C in autosampler tubes, increasing the shelf life to around a month.

Component / Parameter Description / Value

Spray Chamber SilQ Quartz-Cyclonic

Nebulizer SeaSpray™

Torch One-Piece Quartz; 2 mm i.d.

Cones

Pt-tip Sampler

Pt-tip Skimmer

Hyper-Skimmer/OmniRing Assembly

RF Power 1500 W

Plasma Gas Flow 15 L/min

Nebulizer Gas Flow 0.98 – 1.04 L/min

Peripump Speed - 18 rpm

Peripump Tubing for Carrier

Solution Black/Black

Sample Loop Size 1.5 mL

Scan Modes MS/MS and Mass Shift

Resolution Q1/Q3 0.7 amu

Sweeps/Reading 15

Dwell Time 20 - 50 ms

Replicates 3

Integration Time 300 - 750 ms

Reaction Gas Flow 1.1 mL/min O2 ; 0.6 mL/min NH3

Calibration External (matrix matched)

Analysis Time ca. 2 min

Table 1. Instrumental Parameters.

After reconstitution with water, the calibrator is treated in the same way as a patient sample. The calibration is carried out daily for target analytes including Al, Sb, As, Ba, Be, Bi, Cd, Cr, Co, Au, I, Fe, Li, Mg, Mn, Hg, Mo, Ni, Pd, P, Se, Ag, Tl, Sn, Ti, V and Zn. Only freshly reconstituted material should be used for mercury analysis due to mercury’s volatility and the risk of contamination.

Calibration Standard Preparation

In principle, a one-point calibration is possible according to the manufacturer; however, it is recommended to perform a threepoint calibration with a blank in order to increase accuracy for low-level analytes. The calibration standards and serum samples are prepared in the acidic diluent. The blank and standards were prepared as shown in Table 2.

Table 2. Calibration Standards Preparation from ClinCal® Serum Calibrator.

Standard Calibrator (µL) Diluent (µL) Dilution Factor

Blank 0 4000 n/a

Std 1 40 3960 1:100

Std 2 100 3900 1:40

Std 3 200 3800 1:20

The concentrations of analytes in all three standards using ClinCal® Serum Calibrator (lot # 1318, 2022-08) are shown in Table 3.

Table 3. Calibration Standards Prepared from ClinCal® Serum Calibrator.

Matrix: Serum (HNO3 0.1%) Serum 3-Point Calibrator LOT 1318

Analyte Unit m/z Target Value Std 1 (1:100) Std 2 (1:40) Std 3 (1:20)

Lithium (Li) mg/L 7/7 11.0 0.110 0.275 0.550

Beryllium (Be) µg/L 9/9 19.0 0.19.0 0.475 0.950

Magnesium (Mg) mg/L 26/26 30.8 0.308 0.770 1.54

Aluminum (Al) µg/L 27/27 78.3 0.783 1.958 3.915

Titanium (Ti) µg/L 48/114 48.1 0.481 1.203 2.405

Vanadium (V) µg/L 51/51 9.74 0.097 0.244 0.487

Chromium (Cr) µg/L 52/52 7.43 0.074 0.186 0.372

Manganese (Mn) µg/L 55/55 9.89 0.099 0.247 0.495

Iron (Fe) mg/L 56/56 1.96 0.02 0.049 0.098

Cobalt (Co) µg/L 59/59 7.47 0.075 0.187 0.374

Nickel (Ni) µg/L 60/60 7.97 0.08 0.199 0.399

Copper (Cu) mg/L 65/65 1.79 0.018 0.045 0.09

Zinc (Zn) mg/L 66/66 1.7 0.017 0.043 0.085

Arsenic (As) µg/L 75/91 28.3 0.283 0.708 1.415

Selenium (Se) µg/L 80/96 132 1.32 3.30 6.60

Molybdenum (Mo) µg/L 95/95 7.63 0.076 0.191 0.382

Palladium (Pd) µg/L 105/105 29.5 0.295 0.738 1.475

Silver (Ag) µg/L 107/107 28.7 0.287 0.718 1.435

Cadmium (Cd) µg/L 111/111 7.59 0.076 0.19 0.38

Tin (Sn) µg/L 118/118 18.3 0.183 0.458 0.915

Antimony (Sb) µg/L 121/121 11.6 0.116 0.290 0.580

Iodine (I) µg/L 127/127 103 1.03 2.58 5.15

Barium (Ba) µg/L 138/138 206 2.06 5.15 10.3

Platinum (Pt) mg/L 195/195 1.32 0.013 0,03 0.07

Gold (Au) µg/L 197/197 768 7.68 19.2 38.4

Mercury (Hg) µg/L 202/202 11.2 0.112 0.280 0.560

Thallium (Tl) µg/L 205/205 8.86 0.089 0.222 0.443

Bismuth (Bi) µg/L 209/209 7.21 0.072 0.180 0.361

Preparation of Controls

The ClinChek® Serum Controls (Level I and Level II) were used in this work. They were reconstituted with 3 mL of deionized water as per instructions. They were mixed thoroughly in the same way as the CliCal® Calibrator and can be stored in a similar way. These reconstituted controls are stable for up to 8 hours at room temperature and should be prepared fresh on a daily basis. 

However, if needed, they can be frozen at -18 °C in autosampler tubes for up to 1 month.

The controls are diluted 1:20 with acidic diluent in the same way as the samples before analysis.

Sample Preparation

The serum samples were diluted with acidic diluent at a ratio of 1:20. 3800 µL of acidic diluent was added to a 15 mL polypropylene (PP) sample tube, followed by the slow addition of 200 µL of the sample to make a total sample volume of 4000 μL. 

The tube is closed and well homogenized using a vortex mixer. 

Internal Standards

The selection of the internal standard in the analytical ICP-MS method is mass-based and depends on the  measurement mode (Standard/STD, Reaction/DRC). 

Methodology

To achieve optimal performance in terms of intensities and background equivalent concentrations (BECs), the analytes were measured either in Focusing (Foc) or Extraction (Ex) ion guide mode. Depending on the element, MS/MS or Mass Shift scan mode was used. Reactions in the Universal Cell with NH3 or O2 are the most effective method for removing spectral interference, either by converting the interfering ions into species with a different mass (MS/MS) or by forming cluster ions with the analyte (Mass Shift) to separate from the interfering ions. 

In Reaction cell mode, ammonia is the most effective cell gas for eliminating the argon, carbon, or chloride-based interferences on chromium, manganese, and other elements, resulting in detection limits in the low-ppt range. On the other hand, oxygen is the most efficient reaction gas for eliminating metal oxide interferences on cadmium (MoO+) and mercury (WO+) by converting these interferences into dioxide ions. In addition, O2 reacts with arsenic (As) and selenium (Se) to form oxides, moving these elements away from their interferences using Mass Shift mode. For high mass elements free of polyatomic interferences, Standard mode is preferred for its higher sensitivity.

In MS/MS mode, Q1 and Q3 are set to the same mass, while in Mass Shift mode, the analyte is measured at a higher mass as a cluster ion, meaning that Q1 and Q3 are set to different masses. 

In addition to the Standard mode, up to four different cell gases can be used; therefore, all analytes can be measured in one analytical run using the same method, as listed in Table 4.

In order to measure the intensities of some high-concentration analytes in a detector-friendly manner, isotope-specific "electronic dilution" by the cell quadrupole, the parameter RPa, was applied in some cases.

Table 4. Calibration Standards Prepared from ClinCal® Calibrator.

Analyte Unit Isotope (Q1/Q3) Scan Mode Cell Mode Gas Dwell Time (ms) IGM RPa RPq IS

Lithium (Li) mg/L 7/7 MS/MS STD -- 25 Foc 0.015 0.25 103Rh

Beryllium (Be) µg/L 9/9 MS/MS STD -- 50 Foc 0 0.25 103Rh

Magnesium (Mg) mg/L 26/26 MS/MS STD -- 20 Foc 0.015 0.25 103Rh

Aluminum (Al) µg/L 27/27 MS/MS DRC NH3 50 Foc 0 0.45 103Rh

Titanium (Ti) µg/L 48/114 Mass Shift DRC NH3 50 Ex 0.016 0.40 103Rh

Vanadium (V) µg/L 51/51 MS/MS DRC NH3 50 Foc 0 0.40 103Rh

Chromium (Cr) µg/L 52/52 MS/MS DRC NH3 50 Foc 0 0.65 103Rh

Manganese (Mn) µg/L 55/55 MS/MS DRC NH3 50 Foc 0 0.45 103Rh

Iron (Fe) mg/L 56/56 MS/MS DRC NH3 50 Foc 0.012 0.45 103Rh

Cobalt (Co) µg/L 59/59 MS/MS DRC NH3 50 Foc 0 0.45 103Rh

Nickel (Ni) µg/L 60/60 MS/MS DRC NH3 50 Foc 0 0.45 103Rh

Copper (Cu) mg/L 65/65 MS/MS DRC NH3 50 Foc 0.010 0.25 103Rh

Zinc (Zn) mg/L 66/66 MS/MS STD -- 50 Foc 0 0.25 103Rh

Arsenic (As) µg/L 75/91 Mass Shift DRC O2 50 Ex 0 0.45 103Rh

Selenium (Se) µg/L 80/96 Mass Shift DRC O2 50 Ex 0 0.45 103Rh

Molybdenum (Mo) µg/L 98/98 MS/MS DRC NH3 50 Foc 0 0.45 103Rh

Palladium (Pd) µg/L 105/105 MS/MS STD -- 50 Foc 0 0.25 103Rh

Silver (Ag) µg/L 107/107 MS/MS DRC NH3 50 Foc 0 0.25 103Rh

Cadmium (Cd) µg/L 111/111 MS/MS DRC O2 50 Ex 0 0.45 103Rh

Antimony (Sb) µg/L 121/121 MS/MS STD -- 50 Foc 0 0.25 103Rh

Iodine (I) µg/L 126/126 MS/MS STD -- 50 Foc 0 0.25 103Rh

Tin (Sn) µg/L 118/118 MS/MS STD -- 50 Foc 0 0.45 185Re

Barium (Ba) µg/L 138/138 MS/MS STD -- 50 Ex 0 0.25 185Re

Platinum (Pt) mg/L 195/195 MS/MS STD -- 50 Foc 0 0.25 185Re

Gold (Au) µg/L 197/197 MS/MS STD -- 50 Foc 0 0.25 185Re

Mercury (Hg) µg/L 202/202 MS/MS DRC O2 50 Ex 0 0.45 185Re

Thallium (Tl) µg/L 205/205 MS/MS STD -- 50 Foc 0 0.25 185Re

Bismuth (Bi) µg/L 209/209 MS/MS STD -- 50 Ex 0 0.25 185Re

Table 5. Method Detection Limits (DLs) in Serum.

Matrix: Serum Original Sample: Serum

Analyte Isotope (Q1/Q3) Cell Mode Typical DL Unit

Lithium (Li) 7/7 STD 0.0004 mg/L

Beryllium (Be) 9/9 STD 0.006 µg/L

Magnesium (Mg) 26/26 STD 0.0016 mg/L

Aluminum (Al) 27/27 STD 0.4000 µg/L

Titanium (Ti) 48/114 DRC 0.1236 µg/L

Vanadium (V) 51/51 DRC 0.0041 µg/L

Chromium (Cr) 52/52 DRC 0.0053 µg/L

Manganese (Mn) 55/55 DRC 0.0099 µg/L

Iron (Fe) 56/56 DRC 0.0001 mg/L

Cobalt (Co) 59/59 DRC 0.0050 µg/L

Nickel (Ni) 60/60 DRC 0.0310 µg/L

Copper (Cu) 65/65 DRC 0.00002 mg/L

Zinc (Zn) 66/66 DRC 0.0001 mg/L

Arsenic (As) 75/91 DRC 0.0111 µg/L

Selenium (Se) 80/96 DRC 0.0100 µg/L

Molybdenum (Mo) 98/98 DRC 0.0037 µg/L

Palladium (Pd) 105/105 STD 0.0069 µg/L

Silver (Ag) 107/107 STD 0.0018 µg/L

Cadmium (Cd) 111/111 STD 0.0030 µg/L

Zinc (Sn) 118/118 STD 0.0059 µg/L

Antimony (Sb) 121/121 STD 0.0110 µg/L

Iodine (I) 127/127 STD 0.0364 µg/L

Barium (Ba) 138/138 STD 0.0067 µg/L

Platinum (Pt) 195/195 STD 0.00002 mg/L

Gold (Au) 197/197 STD 0.0424 µg/L

Mercury (Hg) 202/202 DRC 0.0681 µg/L

Thallium (Tl) 205/205 DRC 0.0012 µg/L

Bismuth (Bi) 209/209 STD 0.0019 µg/L

Results and Discussion

Method Detection Limits

In principle, the method detection limits (MDLs) presented in Table 6 should be considered as guideline values for the

method. Various factors such as the selected dilution factor, instrument conditions, sample handling, cleanliness of equipment and purity of reagents, as well as contamination control of laboratory environment can significantly impact the final results.

The MDLs were calculated as follows:

 MDL in original sample = 3 x SD(Blk) x Conc(Std) / [I(Std) –

I(Blk)] x Dilution Factor

Where: SD is standard deviation averaged from 7 measurements; and I is signal intensity in counts/second.

Calibration Curves

Calibration standards were prepared according to the ratios shown in Table 2 from the ClinCal® Serum Calibrator with the concentrations for each standard listed in Table 3. All calibration curves have correlation coefficients higher than 0.999. Example calibration curves are shown in Figure 1.

Figure 1. Selective calibration curves.

Table 6. Results for ClinChek® Serum Control Level I.

Matrix: Serum (HNO3 0.1%) ClinChek® Serum Control Level I LOT 1399

Analyte Unit Mass Target Value Min Max Actual Value RSD (%) n=3 Recovery (%)

Lithium (Li) mg/L 7/7 3.63 3.08 4.17 3.8 0.2 105

Beryllium (Be) µg/L 9/9 1.95 1.46 2.44 2.00 0.9 103

Magnesium (Mg) mg/L 26/26 16.1 14.5 17.7 15.6 0.6 97

Aluminum (Al) µg/L 27/27 16.9 11.8 21.9 15.8 1.1 93

Titanium (Ti)* µg/L 48/114 -- -- -- -- -- --

Vanadium (V) µg/L 51/51 2.17 1.74 2.60 2.00 0.2 92

Chromium (Cr) µg/L 52/52 1.59 1.20 1.99 1.80 0.4 113

Manganese (Mn) µg/L 55/55 2.43 1.82 3.04 2.60 0.7 107

Iron (Fe) mg/L 56/56 0.83 0.70 0.95 0.80 0.4 97

Cobalt (Co) µg/L 59/59 2.00 1.60 2.40 2.20 0.4 110

Nickel (Ni) µg/L 60/60 2.05 1.54 2.57 2.13 3.9 104

Copper (Cu) mg/L 65/65 0.74 0.63 0.85 0.81 0.2 109

Zinc (Zn) mg/L 66/66 1.03 0.88 1.19 1.07 0.9 104

Arsenic (As) µg/L 75/91 9.45 7.09 11.8 9.42 0.7 100

Selenium (Se) µg/L 80/96 54.8 43.9 65.8 53.2 2.0 97

Molybdenum (Mo) µg/L 95/95 1.82 1.36 2.27 1.99 1.5 109

Palladium (Pd) µg/L 105/105 5.07 3.55 6.59 5.0 0.9 99

Silver (Ag) µg/L 107/107 4.93 3.94 5.91 5.11 0.9 104

Cadmium (Cd) µg/L 111/111 1.91 1.34 2.48 1.85 1.7 97

Tin (Sn) µg/L 118/118 2.00 1.50 2.50 2.10 2.7 105

Antimony (Sb) µg/L 121/121 3.60 2.88 4.31 3.70 1.5 103

Iodine (I) µg/L 127/127 40.0 32.0 47.9 39.5 0.4 99

Barium (Ba) µg/L 138/138 70.2 56.1 84.2 67.6 1.4 96

Platinum (Pt) mg/L 195/195 0.265 0.21 0.318 0.3 0.7 102

Gold (Au) µg/L 197/197 97.4 73.0 122 97.6 1.4 100

Mercury (Hg) µg/L 202/202 2.03 1.63 2.44 2.00 2.5 99

Thallium (Tl) µg/L 205/205 1.79 1.43 2.14 1.81 1.7 101

Bismuth (Bi) µg/L 209/209 0.944 0.708 1.18 1.00 1.7 106

Accuracy

In order to validate the method, serum control materials (ClinChek®) of different concentrations, namely Level I and Level II, were investigated.

The analyte concentrations in the control samples are present at concentrations in the lower and medium occupational medical-toxicological measurement ranges. Triplicate determinations were performed from one vial, and the corresponding mean values and the relative standard deviation (RSD) were assessed as intra-assay precision. Tables 6 and 7 show the measured values, the target values and control ranges specified by the manufacturer for Level I and Level II, respectively. For all target elements, the measured values are well within the specified ranges with recoveries between 92% and 113%, demonstrating the accuracy and suitability of this method for serum analysis.

* Ti not certified in this CRM

Table 7. Results for ClinChek® Serum Control Level II.

Matrix: Serum (HNO3 0.1%) ClinChek® Serum Control Level II LOT 1399

Analyte Unit Mass Target Value Min Max Actual Value RSD (%) n=3 Recovery (%)

Lithium (Li) mg/L 7/7 7.16 6.09 8.23 7.81 0.7 109

Beryllium (Be) µg/L 9/9 9.6 7.68 11.5 10.2 0.7 106

Magnesium (Mg) mg/L 26/26 21.4 19.3 23.5 21.4 1.6 100

Aluminum (Al) µg/L 27/27 58.6 43.9 73.2 55.8 0.2 95

Titanium (Ti)* µg/L 48/114 -- -- -- -- -- --

Vanadium (V) µg/L 51/51 7.74 6.19 9.29 8.20 1.6 106

Chromium (Cr) µg/L 52/52 5.63 4.50 6.75 5.87 2.0 104

Manganese (Mn) µg/L 55/55 6.01 4.81 7.21 6.25 0.6 104

Iron (Fe) mg/L 57/57 1.39 1.18 1.60 1.49 0.2 107

Cobalt (Co) µg/L 59/59 5.41 4.32 6.49 5.62 0.3 104

Nickel (Ni) µg/L 60/60 5.59 4.47 6.70 5.83 5.7 104

Copper (Cu) mg/L 65/65 1.36 1.15 1.56 1.45 1.6 107

Zinc (Zn) mg/L 66/66 1.47 1.25 1.70 1.46 0.3 99

Arsenic (As) µg/L 75/91 18.0 13.5 22.5 18.6 0.5 103

Selenium (Se) µg/L 80/96 110 88.0 132 110 0.3 100

Molybdenum (Mo) µg/L 95/95 5.22 4.17 6.26 5.59 0.2 107

Palladium (Pd) µg/L 105/105 19.1 15.3 22.9 20.1 0.4 105

Silver (Ag) µg/L 107/107 19.0 15.2 22.8 19.4 1.6 102

Cadmium (Cd) µg/L 111/111 5.51 4.41 6.61 5.60 0.1 102

Tin (Sn) µg/L 118/118 9.15 7.32 11.0 9.40 1.0 103

Antimony (Sb) µg/L 121/121 8.60 6.88 10.3 9.02 1.1 105

Iodine (I) µg/L 127/127 76.4 61.0 91.7 76.0 0.7 99

Barium (Ba) µg/L 138/138 158 127 190 158 0.7 100

Platinum (Pt) mg/L 195/195 0.866 0.690 1.04 0.91 0.8 105

Gold (Au) µg/L 197/197 470 376 564 487 0.8 104

Mercury (Hg) µg/L 202/202 7.37 5.90 8.85 7.61 1.0 103

Thallium (Tl) µg/L 205/205 6.86 5.49 8.24 7.21 0.2 105

Bismuth (Bi) µg/L 209/209 4.48 3.59 5.38 4.63 1.7 103

* Ti not certified in this CRM

Conclusion

The innovative design of PerkinElmer’s NexION 5000 multiquadrupole ICP-MS allows accurate and fast determination of major and trace inorganic compounds in serum after a simple sample preparation. The advanced capabilities of the NexION 5000 ICP-MS have significantly enhanced the accuracy and efficiency of elemental analysis. This is attributed to the instrument’s two distinct features: (1) two full-resolution analyzer quadrupoles to provide precise ion filtering and measurement; and (2) the ability to leverage both Collision and Reaction modes within the proprietary Universal Cell Technology (UCT) to effectively remove spectral interferences. These features collectively ensure that the NexION 5000 ICP-MS delivers high sensitivity and specificity in detecting trace elements, even in complex matrices like serum. The NexION 5000 ICP-MS thus represents a substantial improvement in the field of mass spectrometry, offering users a powerful tool for achieving reliable and reproducible results.

Elemental Analysis of Serum Using the NexION 5000 ICP-MS

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Component Part No.

Nebulizer: SeaSpray (0.4 mL/min) N8151070

Spray Chamber: SilQ Quartz Cyclonic N8152424

Torch: One-Piece Quartz with 2.0 mm i.d. Injector N8152472

Pt-tip Sampler Cone N8161140

Pt-tip Skimmer Cone W1033614

Hyper-Skimmer/OmniRing Assembly N8160120

HTS Loop: 1.5 mL N8152932

Carrier Tubing: Black/Black (0.76 mm i.d.), PVC, Flared N8152407

Drain Tubing: Gray/Gray (1.30 mm i.d.) Santoprene N8152415

Single-Element Standard: Rhenium, 1000 mg/L (125 mL) N9303793

Single-Element Standard: Rhodium, 1000 mg/L (125 mL) N9303794

Autosampler Tubes, 15 mL B0193233

Consumables Used

Appendix A – Basic Diluent

Reagents

Water

Reason for application: Water is the most important solvent and dilution reagent and should be of the highest purity. Milli-Q water with resistance of > 18 MΩ is advantageous.

Ammonia Hydroxide

Reason for application: Basic reagents stabilize cells and prevent protein coagulation. Recommended: high-purity Suprapur™ (Sigma-Aldrich) or comparable.

2-Propanol/Butanol

Reason for application: Acts as a carbon buffer for standards and various chemical matrices. Improves the excitability of the elements such as arsenic (As) and selenium (Se) in the plasma.

TERGITOL™ 15-S-9

Reason for application: Better wettability of the sample introduction system.

EDTA (H+ Form)

Reason for application: Reagent for complexing the metals in alkaline solution.

Example Basic Diluent 

Dissolve 0.5 g EDTA (H+ form), 10 mL isopropanol, 10 mL ammonia hydroxide (25%) and 10 μL each of a 1 g/L Rh and 1 g/L Re solution as an internal standard (IS; concentration = 10 μg/L) in a 1 L PTFE bottle in some deionized water. Then add 0.5 g of a 10% TERGITOL™ solution, mix well (concentration = 0.005%) and make up to 1 L with deionized water. Shelf life at room temperature is approximately 3 days.

Autosampler Solutions

When working in an alkaline medium, the rinsing stations in the ICP-MS autosampler should not contain any acids but should always be rinsed with alkaline medium to prevent unwanted precipitation or coagulation of the urine matrix in the autosampler probe and to prevent clogging of the nebulizer. The basic diluent solution without internal standards (IS) should be used as the rinsing and carrier solution (carrier) when using an automatic loop sample feeding system (HTS, FAST).

Appendix B – Recommended Sequence of ICP-MS Analysis

1. 3 - 5 times 0.1% HNO3 or clinical diluent (basic) for conditioning the system

2. A blank and corresponding calibration standard (urine calibrator)

3. 3 times 0.1% HNO3 or clinical diluent (basic)

4. QC samples (ClinChek® Controls)

5. Urine patient samples

6. 3 times rinsing solution (15% H2O2) for dissolving organic compounds adsorbed in the sample introduction system

7. 2 times 0.1% HNO3 or clinical diluent (basic)

8. 2 times deionized water