Supplemental Materials Table S-3. Comparison of Limit of Detection Differences by Preparation Method and Analytical Platform for 9 Replicate Analyses.

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Supplemental Materials Table S-3. Comparison of Limit of Detection Differences by Preparation Method and Analytical Platform for 9 Replicate Analyses of a Single Serum Sample Spiked with 0.5 µg Co/L Co Conc. by ICP-CRC-MS (µg/L) Co Conc. by ICP-DRC-MS (µg/L) Co Conc. by ICP-CRC-MS (µg/L) Co Conc. by ICP-DRC-MS (µg/L) Preparation MethodAcid Digestion Detergent Dilution Mean Serum Co Conc. with No Spike Replicate Replicate Replicate Replicate Replicate Replicate Replicate Replicate Replicate Corrected Mean + SD Limit of Detection Corrected mean is the average of each replicate Co concentration after subtracting the mean value with no spike (n = 9). Limit of detection is determined according to the analytical solution detection limit (ASDL) calculation reported by the Association of American Chemists: ASDL = 2 x t0.95 x SqrRt [1+(1/n-1)] x SD Where: t 0.95 = one-sided Student's t at 95% confidence level; n = number of replicates; SD = standard deviation of replicates.

Supplemental Materials Table S-4. Comparison of Pre-Spiked/Frozen Serrum Co Concentrations by Preparatory Method and Mixing Status After Thawing Serum Code Co Spike Conc. (µg/L) Co Conc. by ICP-DRC-MS (µg/L) Mean + SD Relative Percent Difference (%) Unmixed/Detergent DilutionMixed/Acid Digestion % % % % % % % % % % % % ICP-DRC-MS was operated without DRC correction and reported Co concentrations were not adjusted for 0 ug/L spike value. Mean values are based on n = 3. Each serum sample was mixed after initial Co spiking and then frozen for 8 days, then aliquots were taken with or without mixing; an aliquot was prepared by detergent dilution without mixing the thawed sample, and another aliquot after mixing was prepared by acid digestion. Comparison of mean values between the two test conditions revealed no significant differences using the unpaired Student's t-test with a significance criterion at p < 0.05.

Supplemental Materials Table S-5. Interference Removal Comparison for Three Serum Sources Between Dynamic Reaction Cell and Collision Reaction Cell Technologies Serum Code Co Spike Conc. (µg/L) Co Conc. By ICP-CRC- MS (µg/L) Mean + SD Co Conc. By ICP-DRC- MS (µg/L) Mean + SD Cell gasNoneHelium NoneAmmonia (RPq = 0.6)Ammonia (RPq = 0.7)Ammonia (RPq = 0.8) Ammonia (RPq = 0.85) Cell Gas FlowNot Applicablelowhigh

Supplemental Materials Table S-6. MS-MS Data for Serum Samples from ICP-QQQ-MS Transition Blank10 ppb 200 ppm Ca,MgBlank Serum Code 1 Serum Code > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 43 Ca [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 44 Ca [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS > 59 [ NH3 Scan ]CPS CPS = Counts per second

Supplemental Materials Table S-7. Comparison of Limit of Detection Differences by Analytical Platform for 9 Replicate Analyses of a Single Whole Blood Sample Spiked with 0.5 µg Co/L Co Conc. by ICP-CRC-MS (µg/L)Co Conc. by ICP-DRC-MS (µg/L) Preparation MethodAcid Digestion Mean Serum Co Conc. with No Spike Replicate Replicate Replicate Replicate Replicate Replicate Replicate Replicate Replicate Corrected Mean + SD Limit of Detection Corrected mean is the average of each replicate Co concentration after subtracting the mean value with no spike (n = 9). Limit of detection is determined according to the analytical solution detection limit (ASDL) calculation reported by the Association of American Chemists: ASDL = 2 x t0.95 x SqrRt [1+(1/n- 1)] x SD Where: t 0.95 = one-sided Student's t at 95% confidence level; n = number of replicates; SD = standard deviation of replicates.

Supplemental Materials Table S-8. Interference Removal Comparison for Three Whole Blood Sources Between Dynamic Reaction Cell and Collision Reaction Cell Technologies Whole Blood Code Co Spike Conc. (µg/L) Co Conc. By ICP-CRC- MS (µg/L) Mean + SD Co Conc. By ICP-DRC- MS (µg/L) Mean + SD ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 40.3 Cell gasNoneHelium NoneAmmonia (RPq = 0.6)Ammonia (RPq = 0.7)Ammonia (RPq = 0.8) Ammonia (RPq = 0.85) Cell Gas FlowNot Applicablelowhigh