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Renewal of NIST Benchmark SRMs for Accurate Determinations of Trace Elements in Serum and Liver Tissues


The Centers for Disease Control and Prevention (CDC) collects data on elemental composition of human body fluids and tissues as part of major studies such as the National Health and Nutrition Examination Survey (NHANES). These studies require the analysis of large numbers of samples obtained from the study subjects. Accuracy of the analytical data is critical and must be assured with proper quality control materials. NIST has supported clinical trace element measurements with several benchmark SRMs, the supplies of two of which, SRM 1598 Bovine Serum and SRM 1577b Bovine Liver, have been exhausted. Replacement materials, SRM 1598a Animal Serum and SRM 1577c Bovine Liver, have been issued. Emphasis on assigning certified or reference values for of all of CDC’s priority elements increased the value to these renewal materials.


NIST has maintained two benchmark materials, a fresh-frozen animal serum SRM and a freeze-dried powdered bovine liver tissue, SRM 1598 Bovine Serum and SRM 1577b Bovine Liver, respectively. The renewals of these materials had to address the challenges of very low levels of trace elements typically present in uncontaminated biological tissues, the changes in available analytical techniques compared with those available for use in the certification of the original serum and bovine liver SRMs, and the addition of new elements of interest.  The Centers for Disease Control and Prevention (CDC) have identified ten elements of interest in their efforts to monitor the U.S. population’s health and nutritional status, which together with a selection of elements with known toxicological effects formed the target for the analytical characterization. The delivery of the two materials with an expanded list of elements certified at naturally occurring levels establishes a robust benchmark for the measurements of critical elements in human and animal body fluids and tissues.

Additional Technical Details:

SRM 1598a was prepared from a serum pool derived from a mixture of serum from healthy bovine and porcine animals. The sera were collected under strict protocols designed to preserve the original composition and to minimize contamination. Briefly, the blood was obtained directly from an incision of the carotid artery and was collected in clean polyethylene pails. It was then immediately (before clotting) distributed among clean polyethylene bottles for further preparation in a U.S. Department of Agriculture clean room facility. After clotting, purified serum was obtained by centrifugation. Serum collections from individual animals were obtained in July 2003 and stored at 4 °C. The serum samples were pooled, and 5 mL aliquots were dispensed into pre-cleaned polypropylene tubes, which were capped and frozen at –80 °C.

For the renewal material SRM 1577c, liver tissue had been collected from 31 steers that were slaughtered at Texas A&M University School of Veterinary Medicine.  Each liver was rinsed with HPLC-grade water to remove excess blood, bile, and any other extraneous material. Fresh tissue (120 kg) was harvested from this process, frozen in clean Teflon bags, and shipped to NIST. The tissue was homogenized at NIST with a food processor equipped with titanium blades. The resulting paste was poured into glass trays, frozen, and lyophilized. The dry material was blended in a food processor and then jet-milled. The resulting final product was radiation sterilized, and bottled in 20 g units.

For elemental certification, NIST values for Cd and Ni in serum and Cd, Pb, Se, and Zn in liver were obtained with isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS); all other elements were determined with at least one method carried out at NIST: instrumental (INAA) and radiochemical (RNAA) neutron activation analysis, NAA with pre-concentration of selected elements on Chelex 100 columns (PNAA), ICP-MS, and inductively coupled plasma optical emission spectrometry (ICP-OES). The measurements were complemented by collaborating scientists from research and clinical laboratories using graphite furnace atomic absorption spectrometry (GFAAS), ID gas chromatography (GC)-MS, ICP-MS, ICP-OES, INAA, and RNAA. The CDC priority elements for which certified values are provided are Al, Cr, Cu, Mn, Ni, Se, V, and Zn.

Major Accomplishments:

  • SRMs 1577c and 1598a have been issued.  
  • Advancements in analytical methodology provided assigned values four additional critical elements.    
  • The partnership with government and private scientific institutions in all relevant disciplines achieved the best possible results for the measurement communities.

Start Date:

October 1, 2002

End Date:

October 2008

Lead Organizational Unit:



Steven J. Christopher
Stephen E. Long
Karen E. Murphy
Rabia Oflaz
Rick L. Paul
Savelas Rabb
Laura Wood
Lee Yu

Associated Products:

SRM 1577c Bovine Liver
SRM 1598a Bovine Serum 

Associated Publications:

Zeisler R., Mackey, E. A., Lamaze, G. P., Stover, T. E., Spatz, R. O., and Greenberg, R. R., “NAA methods for determination of nanogram amounts of arsenic in biological samples,” J. Radioanal. Nucl. Chem., 2006, 269, 291-296

Lindstrom, R.M., Zeisler, R., Greenberg, R.R., “Accuracy and Uncertainty in Radioactivity Measurement for NAA,” J. Radioanal. Nucl. Chem., 2007, 271, 311-315

B.E. Tomlin, R. Zeisler, R.M. Lindstrom, “γ-γ Coincidence Spectrometer for INAA”, Nucl. Instr. Meth., A 589 (2008) 243-249

R. Zeisler, W. D. James, E. A. Mackey, R. O. Spatz, R. R. Greenberg, “NAA Characterization of the New Bovine Liver SRM,” J. Radioanal. Nucl. Chem., 2008, 278, 000-000.

R. Zeisler, R. R. Greenberg, E. A. Mackey, K. E. Murphy, R. O. Spatz, B. E. Tomlin, “Challenges and success in the use of neutron activation analysis procedures for value assignment of anaimal serum and bovine liver Standard Reference Materials,” J. Radioanal. Nucl. Chem., in press.


Rolf Zeisler
Phone 301-975-6290

Gregory C. Turk
Phone 301-975-4118