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Between Method/Laboratory MSMS
Analyte Harmonization
Using CDC Quality Control Materials
Mary A. Seeterlin1, E. Stanley1, R. Grier2,
K. Cavanagh1, P. Rinaldo3, V. DeJesus4
1. Michigan Department of Community Health, Lansing, Michigan,
2. Detroit Medical Center, Children’s Hospital of Michigan,
3. Department of Laboratory Medicine and Pathology, Mayo Clinic
College of Medicine, Rochester, Minnesota,
4. Centers for Disease Control and Prevention, Atlanta, GA.
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2009 Directive
Validate PerkinElmer NeoBaseTM Non-derivatized MSMS Kit on Waters TQD
– Previously PerkinElmer NeoGram® Derivatized MSMS Kit on SCIEX 2000
Evaluate cutoffs with respect to R4 target cutoff ranges
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Validation Assessments
Precision
Linearity
Accuracy
• NeoBaseTM Kit Controls
• CDC Quality Control Samples
• Cutoffs: NeoGram-NeoBase Method
Comparison
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332 Normal Patient samples
11 PT Samples
High and Low Kit Controls
True Positive samples
Method Comparison Analysis
NeoGram (μmol/L)
NeoB
ase (
μm
ol/L)
Methionine (Met)
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NeoGram Met Cutoff (74)
Neo
Ba
se M
et
Cuto
ff (
56
)N
eoB
ase (
μm
ol/L)
NeoGram (μmol/L)
Methionine (Met)
NeoBase 0.775 * NeoGram
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Method Comparison Analysis
NeoGram (umol/L)
NeoB
ase (
μm
ol/L)
NeoGram (μmol/L)
Methionine (Met)
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NeoGram Met Cutoff (74)
Neo
Ba
se M
et
Cuto
ff (
56
)
NeoGram (μmol/L)
NeoB
ase (
μm
ol/L)
Method Comparison Analysis
Methionine (Met)
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NeoGram Met Cutoff Equivalent NeoBase Met Cutoff
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Validation Goals
Evaluate Cutoffs
NeoGram/NeoBase Method Comparison
• All MSMS analytes cutoffs evaluated
Region 4 Cutoff Range Comparison:
• Could this Method Comparison technique work
for Between Laboratory Cutoff Comparison?
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Cutoff evaluation with respect to Region 4 target cutoff ranges…
Why do some of our cutoffs not coincide with the R4 target cutoff range?
• Differences in the Methods• Extraction technique• Instrumentation• Internal Standard• Calibration Technique• Standard Calibration Material Use
• (Traceable to National Standards)
• Cutoffs in question are not clinically valid
Cutoffs
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MI NeoGram Cutoff = 74
MI NeoBase Cutoff = 56Target Range
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Better?Target Range
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Better?
Equivalent!
Target Range
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Target Range:
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NeoBase 0.144 * CDC
NeoB
ase (
μm
ol/L)
CDC (μmol/L)
Succinylacetone (SA)
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Mayo (μmol/L)
NeoB
ase (
μm
ol/L)
NeoBase 0.247 * Mayo
Succinylacetone (SA)
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Mayo SUAC Cutoff Equivalent NeoBase SUAC Cutoff
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Mayo SUAC Cutoff Cutoff set to 1.0 (99.99%ile = 0.82)
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NeoBase (μmol/L)
Mayo
(μ
mol/L)
Succinylacetone (SA)
NeoBase 4.051 * Mayo
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TP TYR1: SUAC
Mayo (
μm
ol/L)
NeoBase (μmol/L)
FP TYR1
Succinylacetone (SA)
MI Neobase = 8.76 µmol/L
Mayo = 35.2 µmol/L Mayo = 4.051 * Neobase – 0.29731
Calculated Mayo = 35.2 µmol/L
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NeoGram Cutoff = 0.41
Target Range
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Mayo (μmol/L)
NeoG
ram
(μ
mol/L)
Glutarylcarnitine (C5DC)
NeoGram 5.168 * Mayo
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Mayo C5DC Cutoff Equivalent NeoGram C5DC Cutoff
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Target Range Mayo Cutoff = 0.15
MI Equivalent Cutoff = 0.765
NeoGram Cutoff = 0.41
MI TP GAI: C5DC = 0.46
NeoBase C5DC 99.99%tile = 0.732
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MI Cutoff = 68
Target Range
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Mayo (μmol/L)
NeoG
ram
(μ
mol/L)
Arginine (Arg)
NeoGram 3.550 * Mayo
TP ARGMI = 107 µmol/L
Mayo = 29.5 µmol/L
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Mayo Arg Cutoff Equivalent NeoGram Arg Cutoff
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MI Cutoff = 68
Mayo Cutoff = 25
MI Equivalent Cutoff = 85
Target Range
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Mayo (μmol/L)
NeoG
ram
(μ
mol/L)
Free carnitine (C0)
NeoGram 1.781 * Mayo
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Sample Exchange - 6 months.
Mayo (μmol/L)
NeoG
ram
(μ
mol/L)
Free carnitine (C0)
NeoBase 1.781 * Mayo
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MI N
eoB
ase (
μm
ol/L)
Missouri NeoGram (μmol/L)
Malonylcarnitine (C3DC)
NeoBase 0.096 * Missouri
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MI N
eoB
ase (
μm
ol/L)
Missouri NeoGram (μmol/L)
Malonylcarnitine (C3DC)
TP MAL
MO C3DC = 5.75 µmol/L
MI C3DC = 0.60 µmol/L
MI = 0.096 * MO + 0.0485
Calculated MI = 0.60 µmol/L
NeoBase 0.096 * Missouri
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Harmonization Using CDC Quality Control Materials:
Allows Harmonization of Cutoffs
Allows Harmonization of TP Analyte Concentrations
Conclusions
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Allowed for an accurate comparison of Cutoff Values between Michigan and Mayo.
Identified that C16OH, C0, Cit, Cit/Arg, and Met cutoffs required correction.
Conclusions
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Acknowledgements:
MI NBS Team – Eleanor Stanley
Dr. Robert Grier – CHMMC, BGL
Patrick V. Hopkins – Missouri
Marie-Thérèse Berthier, Quebec – NeoBase
Sheila Weiss/Bill Hoffman – Washington
Dr. Victor DeJesus/CDC Quality Assurance Program
Dr. Piero Rinaldo/David McHugh - Region 4 Collaborative
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NeoB
ase (
μm
ol/L)
CDC (μmol/L)
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CDC equivalent uMol/L
CD
C e
quiv
ale
nt uM
ol/L
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CD
C e
quiv
ale
nt uM
ol/L
?