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Development of SRM 955c Toxic Elements in Caprine Blood


Environmental and occupational exposure to toxic metals is assessed through whole blood analysis. Due to advances in measurement technology, clinical laboratories that perform whole blood analyses are moving away from single-element methods towards methods capable of measuring panels of toxic elements and species. NIST is providing values for inorganic arsenic (As), cadmium (Cd), total mercury (THg), inorganic mercury (iHg), methylmercury (MeHg) and ethylmercury (EtHg) in two levels of the existing Standard Reference Material (SRM) 955c Toxic Elements in Caprine Blood to support method development and provide quality assurance of clinical measurements of toxic metals in blood.  SRM 955c will serve as a replacement for SRM 966 Toxic Elements in Bovine Blood.


NIST issued SRM 966 Toxic Elements in Bovine Blood in 2000. SRM 966 was originally produced at the Centers for Disease Control and Prevention (CDC), and comprises a two level material containing Cd, Pb, THg, iHg, and MeHg. As a consequence of the demand for this reference material, the stock of SRM 966 is rapidly running out. The CDC no longer has the capability to produce a renewal batch of this SRM. An alternative replacement material is SRM 955c Toxic Elements in Caprine Blood, which was issued as Led in Caprine Blood by NIST in 2007 with support from the CDC. SRM 955c is heavily relied upon for quality assurance of clinical blood Pb measurements, and is certified for Pb at four concentration levels: a base level and three progressively elevated levels. When SRM 955c was produced at the Wadsworth Center, New York State Department of Health (NYDOH), it was also spiked with As, Cd, iHg, MeHg, and EtHg. EtHg is a concern because it is a metabolite of Thimersol which has been used as a preservative in vaccines and is being studied in the proposed link between autism and Hg exposure. The toxicity of Hg is highly dependent on the chemical form, necessitating measurement of the specific Hg species. As, Cd, and THg are typically analyzed together as a “heavy metal screen” for diagnosis of acute poisoning utilizing a multi-element analysis method, inductively coupled plasma mass spectrometry (ICP-MS). Half of all blood analyses in the U.S. are performed using ICP-MS. SRM 955c will serve multiple measurement communities and is the first available whole blood CRM with EtHg and As values.

Additional Technical Details:

New ICP-MS-based technologies are being utilized to measure As and Hg species in SRM 955c, Level 1 and Level 3. Gas chromatography (GC) coupled with ICP-MS is being used to measure IHg, MeHg, and EtHg. A GC-ICP-MS chromatogram obtained for SRM 955c Level 3 is shown in Figure 1. Quantification schemes based on speciated isotope dilution and matrix-matched external calibration have already been developed for iHg and MeHg in blood, and research is being conducted to extend these methodologies to the determination of EtHg. Collision cell technology (CCT) ICP-MS coupled with standard additions is being used to mitigate the effects of matrix-based interferences that make it difficult to measure As. Results for the newly developed CCT ICP-MS method will be compared to results obtained using neutron activation analysis (NAA). A highly sensitive and accurate method based on isotope dilution cold vapor (ID CV) ICP-MS developed at NIST is being used to measure THg. The accurate determination of Cd by ID ICP-MS is complicated by matrix-based interferences that cannot be resolved instrumentally and matrix separation is often required. However, separation procedures can lead to greater uncertainty from contamination. As a result, separations were not used for prior measurement of Cd in SRM 966. Research is being conducted to develop a separation scheme for Cd in SRM 955c at reduced contamination levels.

Major Accomplishments:

  • Developed new method for As by CCT-ICP-MS.
  • Completed NIST certification measurements for As by CCT-ICP-MS, THg, and Cd.
  • Separation scheme developed for ID ICP-MS determination of Cd resulted in a five-fold decrease in uncertainty compared to previous certification of SRM 966.
  • Conducted trial analyses of IHg, MeHg, and EtHg.

Chromatogram of separation of lead species in caprine blood

Start Date:

October 1, 2007

End Date:


Lead Organizational Unit:



Colleen E. Bryan
W. Clay Davis
Stephen E. Long
John Molloy
Karen E. Murphy

Associated Products:

SRM 955c Toxic Elements in Caprine Blood
SRM 966 Toxic Elements in Bovine Blood

Associated publications:

  1. Murphy, K.E., Vetter, T., Turk, G.C., Palmer, C.D., Lewis Jr., M.E., Geraghty, C.M., Parsons, P.J., and Guthrie, W., "Comparison of Clinical Methods with Isotope Dilution ICP-MS for the New Standard Reference Material 955c Lead in Caprine Blood," J. Anal. At. Spectrom., 24: 1170–1178 (2009).
  2. Murphy, K.E., Long, S.E., and Vocke, R.D., On The Certification of Cadmium at Trace and Ultra-Trace Levels in Standard Reference Materials Using ID ICP-MS, Anal Bioanal Chem, 387:2453-2461, (2007).
  3. Zeisler, R., Mackey, E.A., Lamaze, G.P., Stover, T.E., Spatz, R.O., and Greenberg, R.R., J. Radioanal. Chem., 269: 291-296 (2006).
  4. Christopher, S.J., Long, S.E., Rearick, M.S., and Fassett, J.D., Development of High Accuracy Vapor Generation Inductively Coupled Plasma Mass Spectrometry and its Application to the Certification of Mercury in Standard Reference Materials, Anal. Chem., 73:2190-2199 (2001).