Clinical Chemistry AACC Online Job Center
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 43: 2303-2311, 1997;
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hsiung, C.-S.
Right arrow Articles by Ash, K. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hsiung, C.-S.
Right arrow Articles by Ash, K. O.
Related Collections
Right arrow Drug Monitoring and Toxicology
(Clinical Chemistry. 1997;43:2303-2311.)
© 1997 American Association for Clinical Chemistry, Inc.

Articles

Minimizing interferences in the quantitative multielement analysis of trace elements in biological fluids by inductively coupled plasma mass spectrometry

Chiung-Sheng Hsiung1, Joseph D. Andrade1, Robert Costa2 and K. Owen Ash2,a

1 Department of Materials Science & Engineering, University of Utah, Salt Lake City, UT 84112.

2 Department of Pathology and Associated Regional and University Pathologists, 500 Chipeta Way, Salt Lake City, UT 84108.
a Author for correspondence. Fax 801-583-2712; e-mail ASHKO{at}ARUP-lab.com


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results and Discussion
 References
 
The determination of trace and ultratrace elements in biological fluids, including urine and serum, by inductively coupled plasma mass spectrometry (ICP-MS) is discussed. Nonspectral interferences and their corrections by external calibration and calibrator addition are discussed in detail. External calibration with internal calibration and dilution is mostly sufficient to correct for encountered biological matrix effects. For some elements, such as Cs and Zn, the use of calibrator addition provides more accurate results. The importance of spectral interferences and their elimination by isotope selection was also studied. Two examples, Cu and Zn, demonstrate the prime importance of selecting an isotope with minimal polyatomic interferences for analysis. By using 65Cu and 68Zn, accurate results for urine and serum can be obtained without excessive pretreatment of samples. Two reference materials, Bio-Rad Lyphochek urine and Kaulson Contox sera, were analyzed. Accuracy was evaluated by comparison with target values, and precision was estimated by the CV within 95% confidence.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results and Discussion
 References
 
Of the body mass of humans, 98% is made up of nine nonmetallic elements. Trace elements occupy just 0.012% of the body weight of humans (1). However, the determination of trace elements is increasingly crucial since they play important roles in both normal biological function and toxicity (2)(3)(4)(5)(6)(7)(8)(9). Several of these elements are indispensable and essential for life; others and their compounds are simply inert or inocuous at usual exposure concentrations, and others exhibit a high toxicity even in low concentrations. Even essential elements present in too high concentrations may lead to deleterious effects. The reliable monitoring of trace elements has become an important function of many clinical, industrial, and governmental laboratories. Different specimens can be used to best reflect body status. Tissue may be the best specimen but is not easily obtained, and adequate reference information is not available to aid with interpretation of the results. The use of hair is controversial since external contamination is an ever-present problem. Analysis of the relevant elements in biological fluids, either serum/plasma, whole blood, or urine specimen, provides useful information on disturbances of metabolism that involve metals (10)(11)(12)(13)(14)(15).

Analysis of trace elements in biological fluids demands a versatile and reliable technique. The analytical method used must be sensitive, precise, accurate, and relatively fast. Since the first inductively coupled plasma mass spectrometry (ICP-MS) instrumentation was introduced in 1980 (16), this hybrid technique has become an important method for the analysis of trace elements in biological fluids.1 ICP-MS is capable of direct analysis of solution samples with coverage of most elements in the periodic table (17). Moreover, compared with inductively coupled plasma atomic emission spectrometry (ICP-AES), ICP-MS provides much lower detection limits, simpler spectral interpretation, and reliable isotopic analysis (18). Yet, several factors are still of concern in the analysis of trace elements in biological matrices with ICP-MS. Most biological fluids contain large amounts of organic compounds and inorganic salts, which can lead to spectral and nonspectral interferences. Spectral interference occurs because typical ICP-MS instruments use quadrupoles as mass analyzers, which limits the resolution to approximately unit mass. Signals between the analyte and any interferent with a mass larger than the resolution thus cannot be distinguished. Analysis for some elements of biological interest, such as first-row transition metals, as well as As and Se, are thus compromised. Nonspectral interference is a change of signal intensity that cannot be accounted for by recognizable spectral interferences. The interference can be due to either enhancement or suppression. The concentration of the analyte is thus over- or underdetected.

Nonspectral and spectral interferences can seriously affect the analytical performance of ICP-MS. To obtain accurate results for biological fluids, the influences from both interferences must be investigated and eliminated. External calibration and calibrator addition coupled with internal calibration were used to correct for nonspectral interferences. External calibration is based on a set of external calibrators containing elements of interest and internal calibrators in a simple acid. Success in correction of nonspectral interferences depends on the effectiveness of internal calibration. Selection of internal calibrators can be crucial for the accuracy and precision of trace element analysis in biological fluids (19). Calibrator addition is performed by adding increasing quantities of the elements of interest to multiple aliquots of the sample to be analyzed. The calibration set has an identical sample matrix and hence corrects for nonspectral interferences. Internal calibration is preferably combined with calibrator additions to correct for instrumental drift. To eliminate spectral interferences, a careful selection of the analyte isotope is of prime importance. By correctly selecting an isotope with minimal interferences, accurate results can be obtained with no tedious sample pretreatment. Examples of isotope selection for analysis of Cu and Zn are discussed. The feasibility of ICP-MS for direct, quantitative analysis of trace and ultratrace elements in biological fluids is demonstrated by analyzing two reference materials, Bio-Rad Lyphochek urine and Kaulson Contox sera.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results and Discussion
 References
 
reagents and calibrators
All solutions were prepared with trace-grade nitric acid obtained from Mallinckrodt Specialty Chemicals, without further purification, and with reagent-grade deionized water. Metal-free polypropylene (PP) vials and pipette tips were used throughout without precleaning. Plasma quality single-element solution calibrators at 1000 mg/L were obtained from Spex (certified by comparison with NIST SRM 3124a). Stock solutions of internal calibrators, Be and Ga at 1000 µg/L, as well as In and Ir at 500 µg/L, were prepared with 5% nitric acid. Cocktails of multielement calibrators (100 µg/L for each element) were prepared from single-element solutions with 1% nitric acid. Sodium chloride solutions for the study of matrix effects and polyatomic interferences for Cu were prepared by dissolving ACS-grade sodium chloride powder from Fisher Scientific in 1% nitric acid. Analytical reagent-grade sulfuric acid was obtained from Mallinckrodt Specialty Chemicals for study of polyatomic interferences of Zn.

sample preparation
Serum.
The preparation of serum specimens for ICP-MS usually requires a simple dilution (20)(21)(22)(23)(24). However, a precipitation method with nitric acid at room temperature to precipitate protein is preferred in our laboratory; this is important to minimize the occurrence of permanent blockage of the nebulizer, the torch, and the sampling orifice resulting from high concentrations of proteins, as well as to reduce polyatomic ion interferences such as 13C14N on 27Al. The specimen is treated with nitric acid to precipitate proteins and quantitatively release the trace elements, and then diluted with deionized water. The precipitate is removed by centrifugation and the supernatant is used for analysis. Deproteinization should be processed with care to prevent the coprecipitation of trace metals of interest with residues. For some elements, like Fe, precipitation of proteins in plasma or serum with nitric acid is not appropriate because of the low recovery.

Freeze-dried lyophilized serum metals reference materials obtained from Kaulson Lab. were reconstituted with 5 mL of deionized water and 1-mL aliquots placed into 10-mL PP vials with metal-free PP pipette tips. All aliquots were then frozen until used. For analysis, serum was defrosted and a 1-mL stock solution of internal calibrators in 5% nitric acid was added. Protein precipitation occurred upon the addition of internal calibrators, owing to the high nitric acid concentration. The solution was then adjusted to 5 mL with deionized water and centrifuged. The clear supernatant was transferred to another PP vial through a filter for analysis.

Urine.
The specimen preparation required for urine is a simple dilution with nitric acid; then the sample is ready for analysis. The urine is the product of a set of complex processes in the kidneys that removes low-molecular-mass molecules without loss of proteins. Thus, no deproteinization is required unless protein concentration is high; in this case, the precipitate should be removed by centrifugation.

Freeze-dried lyophilized urine metals reference materials obtained from Bio-Rad were reconstituted with 25 mL of deionized water and 1-mL aliquots placed into 10-mL PP vials with metal-free PP pipette tips. All aliquots were then frozen until used. For analysis, urine was defrosted at room temperature. After the addition of 1 mL of stock solution of internal calibrators in 5% nitric acid, the solution was adjusted to 5 mL with deionized water to a final nitric acid concentration of 1%.

instrumentation
The instrument used is a Perkin-Elmer Sciex Elan 5000a ICP-MS equipped with an AS 90 autosampler. A cross-flow nebulizer, a standard Elan torch, and a Scott-type spray chamber were used. Platinum sampling and skimmer cones were used for all studies. Solution uptake was controlled by a peristaltic pump.

To obtain optimum signal intensity for multielement analysis at the trace and ultratrace concentrations, it is necessary to consider the optimization for the entire mass range because optimum ICP-MS instrumental parameters vary from element to element (25). Therefore, three elements, Mg at low mass, Rh at medium mass, and Pb at high mass, at 10 µg/L in a calibrator from Perkin-Elmer, were used to optimize ICP-MS instrumental parameters, including the nebulizer gas flow rate, ion optics voltage, and aerosol injector orifice position relative to the sampling cone, at 1.0 kW power, on a daily basis. By using this three-element optimization, general signal optimization for multielement analysis can be achieved. The instrument operating parameters and the data acquisition parameters are listed in Table 1 .


View this table:
[in this window]
[in a new window]
  		Table 1. ICP-MS instrument operating and data acquisition parameters.


   Results and Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
References
 
For the determination of trace elements in biological materials, additional variables must be considered. Because the metal concentrations in the matrix are extremely low, calibrators and reference materials, as well as the analytical procedure, have to meet very stringent requirements. In biological specimens, the matrix plays an important role. Nonspectral interference can be induced physically and spectral interference can originate from chemical sources. Because interferences can have a large effect on the results, they need to be understood.

nonspectral interferences
Nonspectral interferences in ICP-MS refer to analyte signal intensity changes where the change cannot be accounted for by a recognizable spectral overlap. The analyte signal intensity change can be either a suppression (26)(27) or an enhancement (27)(28)(29)(30)(31)(32). The causes of nonspectral interferences or so-called matrix effects are due to the presence of matrix components. The magnitude of the matrix effects depends on the mass and ionization energy of the matrix elements. It has been reported that the higher the mass of the matrix element, the larger the matrix effects (29)(30)(31)(32). However, high mass matrix elements are rare in biological fluids. For ionization dependence, Olivares and Houk (28) found that the trend of matrix effects was in the order of most easily ionized matrix element, i.e., Na (5.319)>Mg (7.646)>I (10.451)>Br (11.814)>Cl (13.618), where the first ionization energy in eV is noted in parentheses. In contrast, biological specimens contain relatively large concentrations of easily ionized matrix elements, such as Na, K, Ca, and Mg, which makes analysis of these samples difficult. Such matrix effects need to be eliminated to obtain accurate results. Errors associated with matrix-induced signal variation can be corrected by means of an appropriate calibration method. The merits of external calibration with internal calibration and sample dilution, and the alternative strategy of calibrator addition in correction for matrix effects were compared.

external calibration
There are several approaches to overcome matrix effects (33)(34). The most widely used calibration method is by a set of external calibrators containing elements of interest and internal calibrators in a simple acid. Several calibrator solutions are needed to cover the range of expected analyte concentrations. The success of external calibration to correct for matrix effects depends on the effectiveness of internal calibration and dilution of samples.

internal calibration
The calibration or correction of one element by using a second as a reference point has been used in a variety of analytical atomic spectrometry and is termed "internal calibration." An element with a known concentration is added to all solutions, including the blank, calibrators, and unknowns. The analyte signal is then normalized to the signal of the internal calibrator. The effectiveness of an internal calibrator requires that its behavior accurately reflects that of the elements of interest to be measured. Selection of an internal calibrator is of great importance. Ideally, an internal calibrator should undergo the identical matrix suppression or enhancement as that of the analyte element. However, matrix-induced analyte signal changes are not uniform for all elements, but depend on the mass of the element (21)(35)(36). As a consequence, a close match of the mass number between the analyte and internal calibrator is of prime importance to effectively correct for matrix effects. Fig. 1 shows the effectiveness of the internal calibration in NaCl solutions as a function of NaCl concentration. The Ge signal (line B) is suppressed by NaCl. After normalization to the close-mass internal calibrator 71Ga signal, the 72Ge signal (line A) is then independent of NaCl concentration and comparable with the signal in a solution without NaCl. The matrix effect can thus be effectively corrected by using a suitable internal calibrator with a mass close to that of the analyte element. However, it is obvious that one internal calibrator cannot be used for all elements, since the matrix-induced signal variation is mass dependent. Several internal calibrators should be used over the entire mass range. Yet, using a large number of internal calibrators does not necessarily guarantee more accurate analytical performance. Too many internal calibrators (e.g., 10) may result in a practical problem of selecting internal calibrators and higher errors (37). In general, three or four elements as internal calibrators are considered to be adequate for the multielement analysis (21)(34)(36)(38)(39). However, one internal calibrator still covers a group of analyte elements, even though four internal calibrators are used for the multielement analysis. It is impossible to accurately correct for all elements of interest in that group by one internal calibrator. In addition, even an element with similar chemical and physical properties and similar atomic mass may behave in a different way in certain matrices (34)(40). Therefore, some procedure must be used to improve the deficiency of internal calibration.



View larger version (19K):
[in this window]
[in a new window]
  		Figure 1. Effectiveness of an internal calibrator to correct for signal suppression caused by various NaCl concentrations: A, signal ratio for the analyte 72Ge to the internal calibrator 71Ga and B, signal for the analyte 72Ge.

dilution of sample
Specimen dilution is necessary for ICP-MS analysis of biological samples because large amounts of proteins and salts can cause an irreversible reduction of the analyte signal intensity due to clogging of the nebulizer, torch, sampling, and skimmer orifices. One solution is to dilute biological samples with a solvent before injection. In addition, dilution can also reduce matrix effects while the sample is being measured, since matrix effects are dependent on the absolute amount of matrix element rather than the relative concentration of matrix to analyte (32)(33).

Besides preventing clogging and reducing the matrix effect, dilution is also necessary to improve the accuracy of internal calibration. Fig. 2 illustrates the effectiveness of internal calibration as a function of NaCl concentrations. The Se signal (line B) was largely suppressed by NaCl. Normalizing to the 71Ga internal calibrator, the 82Se signal (line A) is still influenced by NaCl concentrations but the effectiveness of the internal calibration is enhanced when NaCl concentrations are decreased. The effectiveness of internal calibration can be improved by dilution.



View larger version (19K):
[in this window]
[in a new window]
  		Figure 2. Effectiveness of an internal calibrator to correct for signal suppression caused by various NaCl concentrations: A, signal ratio for the analyte 82Se to the internal calibrator 71Ga and B, signal for the analyte 82Se.

calibrator addition
Calibrator addition is performed by adding increasing quantities of the elements of interest to multiple aliquots of the sample to be analyzed. The calibration set therefore consists of several supplemented samples plus an unsupplemented original sample, all of which have an identical matrix. Matrix effect is corrected for and highly accurate and precise data can be produced. Internal calibration is also included to correct for instrumental drift.

From a practical viewpoint, external calibration with internal calibration and dilution is most attractive for routine application since it is less time consuming and results in less introduction of matrix materials into the instrument than the other calibration methods. However, the use of calibrator addition provides a way to evaluate the accuracy of external calibration and is sometimes necessary to compensate for the insufficiency of external calibration. External calibration is shown to be adequate to correct for encountered biological matrix effects for most elements. (Data are discussed later.) Yet, external calibration was inadequate for some elements, such as Cs and Zn. For Cs the results obtained for reference urine levels I and II from external calibration, with In as the internal calibrator, are only 67.32% and 68.65% of those from calibrator additions, probably due to the large mass difference between 133Cs and 115In. However, insufficient correction for 68Zn via external calibration was also observed, even with the close-mass internal calibrator 71Ga. The results for both urine and serum reference materials (data shown in Tables 4 and 5 ) from external calibration were located in the very low end of acceptable ranges and the recoveries were poorer than those from calibrator addition. On the other hand, a better agreement between calibrator additions and target values was found. The insufficient corrections for Zn are probably caused by the discrepancy of the first ionization potential between the analyte and the internal calibrator: Zn (9.394 eV) and Ga (5.99 eV). Even after fivefold dilution, internal calibration was still ineffective for the correction of the remaining signal suppression. Calibrator addition is thus an improvement over external calibration for those elements.


View this table:
[in this window]
[in a new window]
  		Table 4. Multielement analysis of Bio-Rad Lyphochek urine Level I and Level II.


View this table:
[in this window]
[in a new window]
  		Table 5. Multielement analysis of Kaulson Contox serum Level I and Level II.

spectral interferences
Spectral interferences can be a major limitation since most ICP-MS units are equipped with a quadrupole mass analyzer that limits the resolution to approximately unit mass. Therefore, ions with the same nominal mass as the analyte, resulting from singly charged ions, doubly charged ions, and polyatomic ions, cannot be resolved. Polyatomic interferences, resulting from combination of precursors in the Ar plasma, entrained atmospheric gases, reagents, or biological matrices, are more problematic. Elements >82 amu are essentially free of polyatomic interferences and suitable for ICP-MS analysis, but elements between 40 and 82 amu can be compromised by these interferences. Accurate analytical results require that spectral interferences be identified and then avoided or corrected.

choice of the isotope
The polyatomic interferences can be avoided in different ways (24)(33)(34). A simple way is to carefully select an isotope for analysis free from significant interferences. An accurate and precise result can thus be obtained. To eliminate the interferences effectively, the encountered polyatomic ions must be identified and the extent of these interferences must be assessed. Since it is impossible to address all polyatomic interferences for every element of interest, only Cu and Zn are discussed to illustrate that the correct choice of the available analyte isotope is of prime importance to obtain an accurate result and minimize the interference.

determination of cu
Cu has two stable isotopes: 63Cu (69.09%) and 65Cu (30.91%). The determination of Cu is complicated because of polyatomic ion interferences from Na at mass 63 (40Ar23Na) as well as from Ca and S at mass 65 (48Ca16OH, 48Ca17O, 33S16O16O, 32S16O17O, 32S33S), where Na, Ca, and S are abundant in biological fluids. Table 2 shows the results of Cu analysis on urine and serum reference materials with masses 63 and 65 under external calibration and calibrator addition. For Bio-Rad Lyphochek urine levels I and II, the results under both calibrations and historically established values by the former method of ARUP with 63Cu were higher than the target values. 63Cu signals were largely influenced by the spectral overlap of 40Ar23Na since the Cu concentration in this sample is low. On the other hand, the determinations made at mass 65 showed excellent agreement. The polyatomic ions at mass 65, from S or Ca, do not result in significant interferences. For Kaulson Contox serum levels I and II, because the serum Cu concentration range is high the signal at mass 63 is not as susceptible to 40Ar23Na interference. However, the results by 63Cu under calibrator additions are still too high. Again the determination made at mass 65 agreed well with the target values. Therefore, we can conclude that the ICP-MS Cu method based on the isotope 65 is suitable for analysis of urine and serum and avoids the major interference.


View this table:
[in this window]
[in a new window]
  		Table 2. Results of Cu analysis in Bio-Rad Lyphochek urine and Kaulson Contox serum.

determination of zn
Zn has five stable isotopes: 64Zn (48.89%), 66Zn (27.81%), 67Zn (4.11%), 68Zn (18.56%), and 70Zn (0.62%). Different Zn isotopes, including 64Zn (36), 66Zn (20)(22)(23)(24)(36)(41), and 68Zn (21), have been attempted for Zn determination in the biological fluids.

The determination of Zn in body fluids can be complicated by the different degrees of S-containing interferences on the Zn isotopes (Table 3 ) (21). Fig. 3 gives the apparent concentration of Zn at masses 64, 66, 67, and 68 as a function of sulfuric acid concentrations. The apparent Zn concentrations at masses 64, 66, and 67 increase linearly with the sulfuric acid concentration. The S-containing polyatomic ions interfere at mass 64 and to a lesser extent at masses 66 and 67. Only mass 68 shows no interference due to S. S-containing polyatomic ions at mass 68 were not detected. This means determination of Zn with masses 64, 66, and 67 may be compromised by S interferences, and mass 68 is more suitable for analysis. The agreement between the target values and the results for urine and serum reference materials with 68Zn is illustrated in Table 4Up and Table 5Up . The results obtained by external calibration are in poorer agreement with the target values than calibrator addition because of the occurrences of matrix suppression. However, the results indicate that 68Zn is generally suitable for body fluids. The use of 68Zn for routine clinical analysis is recommended to completely eliminate the interferences from S, leading to falsely higher results with 64Zn and 66Zn.


View this table:
[in this window]
[in a new window]
  		Table 3. S-containing potential polyatomic interferences for the determination of Zn.



View larger version (18K):
[in this window]
[in a new window]
  		Figure 3. Apparent Zn concentration at masses 64, 66, 67, and 68 as a function of H2SO4 concentration.

analysis of urine and serum reference materials
Table 4Up and Table 5Up summarize the results of multielement analysis obtained on a reconstituted solution of the Bio-Rad Lyphochek urine and Kaulson Contox serum reference materials, respectively. For all reference materials, both external calibration and calibrator addition were applied for analysis. Four internal calibrators were used for multielement coverage: 9Be for low masses; 71Ga for first transition metals as well as for As, Se, Rb, and Sr; 115In for medium masses; and 193Ir for high masses. In consideration of balancing the requirement of high sensitivity for ultratrace concentrations and reduction of matrix effects, a fivefold dilution was applied. The isotopes measured and internal calibrators used are given together with the analytical results within 95% confidence limits. For urine, each result is based on three sample aliquots, analyzed with three repeats, for a total of nine measurements. The results are compared with the target values verified by atomic absorption spectrometry (AAS). For serum, each result is based on two sample aliquots, analyzed with three repeats, for a total of six measurements. The results are compared with the target values referenced by AAS.

In urine, for eight trace elements (As, Cd, Co, Cu, Mn, Ni, Pb, Sb), the results obtained from both calibration methods are in good agreement with target values. For Zn the results obtained from calibrator addition are in better agreement with the target values than external calibration. For Al the results are at the lower end of certified acceptable ranges. For Se the results are higher than the acceptable target ranges, except level II with calibrator addition. However, in comparison with the values, level I: 76.50 ± 5.51 µg/L and level II: 229.25 ± 16.56 µg/L obtained by ARUP, in which the methodology was verified by interlaboratory correlation with certified AAS methods (42), the agreement is excellent. For Tl the results are lower than the acceptable target ranges but in good agreement with ARUP's values (level I: 8.38 ± 0.52 µg/L; level II: 167.43 ± 6.95 µg/L). For seven other elements (Bi, Cs, Mo, Rb, Sn, Sr, W) no data are available for the comparison.

In serum, the results obtained for level II agreed with the target values, except for Mn under external calibration. The results obtained for level I agreed with the target values, except for Ni and Bi. For Ni the results were higher than the target value, which is probably because the signal at mass 60 is susceptible to the 44Ca16O interference at low concentration. For Bi the concentration was lower than the detection limit.

precision
Precision is evaluated by the CV of the repetitive analysis of reference urine and serum under external calibration and calibrator additions. Each result is the average of levels I and II and corresponds to 95% confidence limits. For urine most of the elements in calibrator addition have a comparable and higher precision than external calibration. For either calibration method, elements with ultratrace concentrations (<1 µg/L) have poorer precision. Elements with concentrations >1 µg/L have better precision. The imprecision in the collected data is significantly smaller than the uncertainties of the target values. For serum, the precision for both calibration methods is comparable. The use of calibrator addition does not particularly enhance precision over external calibration. For elements Sn and Pb, precision is poorer, especially in level I, owing to the very low concentrations.

In conclusion, ICP-MS is a practical, versatile method for the determination of many trace and ultratrace elements in the clinical laboratory. However, nonspectral and spectral interferences need to be taken into consideration for the analysis of elements in biological matrices. With internal calibrators of close mass, internal calibration is able to effectively correct for encountered nonspectral interferences; however, specimen dilution is still necessary to improve the effectiveness of internal calibration. With four internal calibrators (Be, Ga, In, Ir) across the entire mass range and fivefold specimen dilution, external calibration is able to accurately measure a variety of trace and ultratrace elements in urine and serum, with the exception of some elements (e.g., Cs, Zn) that have a large discrepancy in atomic mass and ionization energy with that of the internal calibrator. Calibrator addition provides an alternative method to compensate for the insufficiency of external calibration and yields more accurate and precise results in certain cases. Spectral interferences can be eliminated by a simple approach of selecting the isotope with minimal interferences. With proper analytical processes, ICP-MS is generally suitable for the routine multielement analysis of body fluids.


   Footnotes
 
1 Nonstandard abbreviations: ICP-MS, inductively coupled plasma mass spectrometry; PP, polypropylene; and AAS, atomic absorption spectrometry.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
 References
 

  1. Kieffer F. In: Merian E, ed. Metals and their compounds in the environment. Weinheim: VCH, 1991:481pp..
  2. O'Dell BL. Bioavailability of trace elements. Nutr Rev 1984;42:301-308. [Medline] [Order article via Infotrieve]
  3. Elinder C-G, Gerhardsson L, Oberdoerster G. Biological monitoring of toxic metals—overview. Clarkson TW Friberg L Nordberg GF Sager PR eds. Biological monitoring of toxic metals 1988:1-71 Plenum Press New York. .
  4. Nielsen FH. Possible future implications of ultratrace elements in human health and disease. Prasad AS eds. Essential and toxic trace elements in human health and disease 1988:277-292 Wiley-Liss New York. .
  5. Nielsen FH. New essential trace elements for the life sciences. Biol Trace Elem Res 1990;:599-611.
  6. Nielsen FH. Trace and ultratrace elements in health and disease. Compr Ther 1991;17:20-26. [Medline] [Order article via Infotrieve]
  7. Nielsen FH. Ultratrace elements of possible importance for human health: an update. Prasad AS eds. Essential and toxic trace elements in human health and disease: an update 1993:355-376 Wiley-Liss New York. .
  8. Menendez-Botet CJ, Schwartz MK. Trace metals. Anal Chem 1991;63:194R-199R.
  9. Savory J, Wills MR. Trace elements: essential nutrients or toxins. Clin Chem 1992;38:1565-1573.
  10. Delves HT. The analysis of biological and clinical materials. Prog Anal Atom Spectrosc 1981;4:1-48.
  11. Delves HT. Assessment of trace element status. Clin Endocrinol Metab 1985;14:725-760. [ISI][Medline] [Order article via Infotrieve]
  12. Nomiyama K, Nomiyama H. Simultaneous determinations of essential trace metals in biological fluids and their significance. Okuda K eds. Automation and new technology in the clinical laboratory 1990:117-122 Blackwell Scientific Publications Oxford. .
  13. Daher RT. Trace metals (lead and cadmium exposure screening). Anal Chem 1995;67:405R-410R. [Medline] [Order article via Infotrieve]
  14. Copeland KR. Trace elements in clinical chemistry. Bishop ML Duben-Engelkirk JL Fody EP eds. Clinical chemistry: principles, procedures, correlations, 3rd ed 1996:279-291 Lippincott-Raven Publishers Philadelphia. .
  15. Mertz W eds. Trace elements in human nutrition and health 1996 WHO Geneva. .
  16. Houk RS, Fassel VA, Flesch GD, Saec HJ, Gary AL, Taylor CE. Inductively coupled argon plasma as an ion source for mass spectrometric determination of trace elements. Anal Chem 1980;52:2283-2289.
  17. Ash KO, Komaromy-Hiller G. Analysis of clinical specimens using inductively coupled plasma mass spectrometry. Wong SHY Sunshine I eds. Handbook of analytical therapeutic drug monitoring and toxicology 1997:107-125 CRC Press New York. .
  18. Barnes RM. Analytical plasma source mass spectrometry in biomedical research. Fresenius J Anal Chem 1996;355:433-441.
  19. Nixon DE, Moyer TP. Routine clinical determination of lead, arsenic, cadmium, and thallium in urine and whole blood by inductively coupled plasma mass spectrometry. Spectrochim Acta 1996;51B:13-25.
  20. Vandecasteele C, Vanhoe H, Dams R, Versieck J. Determination of trace elements in human serum by inductively coupled plasma-mass spectrometry. Biol Trace Elem Res 1990;:553-560.
  21. Vandecasteele C, Vanhoe H, Dams R. Inductively coupled plasma mass spectrometry of biological samples. J Anal At Spectrom 1993;8:781-786.
  22. Vanhoe H, Vandecasteele C, Versieck J, Dams R. Determination of iron, cobalt, zinc, rubidium, molybdenum, and cesium in human serum by inductively coupled plasma mass spectrometry. Anal Chem 1989;61:1851-1857. [Medline] [Order article via Infotrieve]
  23. Vanhoe H, Vandecasteele C, Versieck J, Dams R. Determination of trace elements in a human serum reference materials by inductively coupled plasma mass spectrometry. Mikrochim Acta 1989;III:373-379.
  24. Vanhoe H. A review of the capabilities of ICP-MS for trace element analysis in body fluids and tissues. J Trace Elem Electrolytes Health Dis 1993;7:131-139. [Medline] [Order article via Infotrieve]
  25. Vanhoe H, Dams R, Versieck J. Use of inductively coupled plasma mass spectrometry for the determination of ultra-trace elements in human serum. J Anal At Spectrom 1994;9:23-31.
  26. Date AR, Cheung YY, Stuart ME. The influence of polyatomic ion interferences in analysis by inductively coupled plasma source mass spectrometry (ICP-MS). Spectrochim Acta 1987;42B:3-20.
  27. Beauchemin D, McLaren JW, Berman SS. Study of the effects of concomitant elements in inductively coupled plasma mass spectrometry. Spectrochim Acta 1987;42B:467-490.
  28. Olivares JA, Houk RS. Suppression of analyte signal by various concomitant salts in inductively coupled plasma mass spectrometry. Anal Chem 1985;58:20-25.
  29. Gregoire DC. The effect of easily ionizable concomitant elements on non-spectroscopic interferences in inductively coupled plasma-mass spectrometry. Spectrochim Acta 1987;42B:895-907.
  30. Kawaguchi H, Tanaka T, Nakamura T, Morishita M, Mizuike A. Matrix effects in inductively coupled plasma mass spectrometry. Anal Sci 1987;3:305-308.
  31. Kim Y-S, Kawaguchi H, Tanaka T, Mizuike A. Non-spectroscopic matrix interferences in inductively coupled plasma-mass spectrometry. Spectrochim Acta 1990;45B:333-339.
  32. Tan SH, Horlick G. Matrix-effect observations in inductively coupled plasma mass spectrometry. J Anal At Spectrom 1987;2:745-763.
  33. Evans EH, Giglio JJ. Interferences in inductively coupled plasma mass spectrometry. J Anal At Spectrom 1993;8:1-18.
  34. Dams R, Goossens J, Moens L. Spectral and non-spectral interferences in inductively coupled plasma mass spectrometry. Mikrochim Acta 1995;119:277-286.
  35. Vanhaecke F, Dams R, Vandecasteele C. "Zone model" as an explanation for signal behaviour and non-spectral interferences in inductively coupled plasma mass spectrometry. J Anal At Spectrom 1993;8:433-438.
  36. Gerotto M, Andrea ED, Bortoli A, Marchiori M, Palonta M, Tronocon A. Interference effects and their control in ICP-MS analysis of serum and saline solutions. Microchem J 1995;51:73-87.
  37. Amarasiriwardena CJ, Gercken B, Argentine MD, Barnes RM. Semi-quantitative analysis by inductively coupled plasma mass spectrometry. J Anal At Spectrom 1990;5:457-462.
  38. Mulligan KJ. Feasibility of the direct analysis of urine by inductively coupled argon plasma mass spectrometry for biological monitoring of exposure to metals. J Anal At Spectrom 1990;5:301-306.
  39. Vanhoe H, Versieck J, Moens L, Dams R. Role of inductively coupled plasma mass spectrometry (ICP-MS) in the assessment of reference values for ultra-trace elements in human serum. Trace Elem Electrolytes 1995;12:81-88.
  40. Moens L, Vanhoe H, Vanhaecke F, Goosons J, Campbell M, Dams R. Application of inductively coupled plasma mass spectrometry to the certification of reference materials from the Community Bureau of Reference. J Anal At Spectrom 1994;9:187-191.
  41. Dams R. RNAA as compared to ICP-MS for the analysis of normal human serum. Biol Trace Elem Res 1994;:539-548.
  42. Costa R, Gordon W, Jennison T, Ash KO. Serum selenium quantitation by ICP/MS isotope analysis [Abstract]. Clin Chem 1995;41:S145.



The following articles in journals at HighWire Press have cited this article:


Home page
 J. Nutr.Home page
S. M. Smith, S. A. Mathews Oliver, S. R. Zwart, G. Kala, P. A. Kelly, J. S. Goodwin, and C. B. Dyer
Nutritional Status Is Altered in the Self-Neglecting Elderly
J. Nutr., October 1, 2006; 136(10): 2534 - 2541.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
S. M. Smith, J. E. Davis-Street, J. V. Fesperman, M. D. Smith, B. L. Rice, and S. R. Zwart
Nutritional Status Changes in Humans during a 14-Day Saturation Dive: The NASA Extreme Environment Mission Operations V Project
J. Nutr., July 1, 2004; 134(7): 1765 - 1771.
[Abstract] [Full Text]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hsiung, C.-S.
Right arrow Articles by Ash, K. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hsiung, C.-S.
Right arrow Articles by Ash, K. O.
Related Collections
Right arrow Drug Monitoring and Toxicology

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS