1. The 2015/2016 TNI Standard and the EPA MDL Update
TCEQ 2016
The 2015/2016 TNI Standard and the EPA MDL Update
Richard Burrows, Ph.D.
TestAmerica Inc.

2. A Revision to the Method Detection Limit
EPA published a revision to the 40 CFR Part 136 MDL procedure in the Federal Register on Thursday February 19th 2015
EPA expects that the rule will be finalized in late 2016

3. TNI Chemistry Standard
Revisions to the Detection, Quantitation and Calibration language in TNI Volume 1 Module 4 (Quality Systems for Chemical Testing) are complete and will be incorporated into the TNI 2015/2016 Standard.
The 2015/2016 TNI Standards should be adopted by the States in 2017/2018

4. MDL and TNI revisions!!?? What if they have different requirements?
What if they are implemented at different times?
What if different states adopt the new requirements at different times?
Will I have to have different detection limits for different states?

6. Good News
The revised MDL and TNI Chemistry standards are fully compatible
If you are compliant with the revised EPA MDL then you are also compliant with the current MDL
One exception, discussed later
If you are compliant with the revised TNI Chemistry standard then you are compliant with the current TNI Chemistry standard

7. Details of the Modifications
Initial MDL

8. First, what stays the same?
Fundamental concept is unchanged
What is the lowest result that is qualitatively reliable, i.e., the lowest result that reliably indicates the analyte is in the sample?
Fundamental approach is unchanged
Describe the distribution as Student’s t times the standard deviation of results

9. What is different?
Requires calculation of a MDL based on blanks as well as a MDL based on spikes (the higher of the two becomes the MDL)
Incorporates longer term variance
Includes checks for reasonableness
Works effectively with various quantitation limit concepts and procedures

10. Details, details Spiking level
2-10 times estimated MDL
Run spiked replicates in at least 3 separate preparation and analysis batches
Multiple instruments
At least 2 spike replicates on each instrument
If blanks give ND, MDLB does not apply
Addendum for MDL determined on a specific matrix
No 10X rule
Use all method blanks unless batch was rejected

11. Ongoing verification

12. MDL verification Collect data quarterly Analyze data annually
One spike per instrument (two if only one instrument)
Requirement is detection
Analyze data annually
Recalculate MDL based on last two years spike and blank data
If within factor of 3 (possibly 2) then lab option to leave unchanged or update
If outside that range then update

13. The TNI MDL Requirements

14. 2009 TNI standard requirements for detection limit
“appropriate and relevant for the intended use of the data
“all sample processing and analysis steps shall be included”
“Each target analyte”
Verify with a spike at 1-3 or 1-4 X the LOD – detection above zero
Verification is required on each instrument
Verification is required annually
Only required if reporting below the LOQ
Repeat each time there is a change that affects the sensitivity of the analysis

15. What is the MDL?

16. Lloyd Currie’s original concept
The lowest result that can be reliably distinguished from a blank LD
The lowest amount present in a sample that will reliably give a result that is above LC LQ
The lowest amount that gives quantitative results
Equals the MDL equals the TNI LOD
Not routinely used in environmental testing
(included in the DOD QAPP)
Conceptually, equals TNI LOQ, EPA ML and EPA LLOQ

17. MDL
MDL The method detection limit (MDL) is defined as the minimum measured concentration of a substance that can be reported with 99% confidence that the measured concentration is distinguishable from method blank results
MDL
3.14 x Standard Deviation
MDL 40 CFR Part 136
LC Currie’s Critical Level

18. What the MDL is (and is not):
MDL = Lowest result that can be distinguished from blanks Or, lowest result that means there is actually something in the sample MDL ≠ Lowest amount in a sample that can be reliably detected

19. MDL and Currie’s LD MDL LD
Currie’s LD is the minimum true concentration that is reliably detected (i.e., gives a result above the MDL)
MDL LD
1% chance of false negative
MDL 40 CFR Part 136
LC LD Currie’s Detection Level
0 DL (LODDOD)  DOD

20. What does this mean regarding verification?
MDL can be verified by examining blank results
MDL cannot be verified with spiked samples
(Curries LD could be verified with spiked samples)

21. 2015/16 TNI standard requirements for detection limit
2005/16
“reflect current operating conditions”
“entire analytical process”
“analytes of interest in each test method in quality systems matrix of interest”
“Include data from low level spikes and routine method blanks”
“Include evaluation of false positive rates”
Verification includes a minimum of one low level spike and one blank per quarter per instrument
Verification is only required if reporting below the LOQ
One option is to follow the EPA MDL procedure

22. The TNI LOQ Requirements
Limit of Quantitation

23. 2009 TNI Standard LOQ 2009 standard
Include all sample processing and analysis steps
Verify with analysis of a standard at 1-2 times LOQ
Verify annually, but not required if the LOD was determined or verified on that instrument
No way to determine precision and accuracy

24. 2015/16 TNI Standard LOQ requirements
2016
At least 3X the MDL
All processing steps
Above lowest calibration standard
Verification (initial)
At least 7 spikes at of below the LOQ
3 batches on 3 separate days
Distribute across instruments, at least 2 per instrument
Results must meet identification criteria and be above zero and within the laboratory established recovery criteria

25. LOQ verification Ongoing
One verification sample on each instrument each quarter
Must meet identification criteria and be above zero
Once per year compile the data and create a statement of precision and accuracy

26. How Does This All Fit Together?

27. TNI LOQ and EPA MDL MDL LOQ Initial 7 spikes
3 separate batches 3 separate days
2 per instrument
Ongoing
One spike per inst. per quarter
One spike per inst. per quarter (2 if only one inst.)
Meet qualitative ID, above zero

28. TNI LOQ and EPA MDL Annual calculation requirement is different: MDL
Calculate MDL(s) as Students t x Standard Deviation
LOQ
Create statement of precision and accuracy
We will see how this works out in the next Section

29. Why Do we need a MDL and a LOQ?

30. Reason #1 that we need MDLs
We need to make the Quantitation limit meaningful
Applies to MRL, LLOQ, or any quantitation limit
Without a MDL, a true concentration at or close to the LOQ is probably going to be reported as a false negative
In other words, without a MDL, our quantitation limit is not only not quantitatively reliable, it is not qualitatively reliable either

31. 90% recovery, 9% RSD Spike #1 #2 #3 #4 #5 #6 #7 Mean MDL 10 9 8.3 9.8
9.3
8.1
8.6
10.0
9.0
2.29
Spike True Value = LLOQ
MDL = 2.29
Calculated MDL
Reported results (without MDL) ND 10

32. If you don’t report below the LOQ you have a lot of false negatives
Bottom Line
If you don’t report below the LOQ you have a lot of false negatives
You can’t minimize false negatives and false positives at the same level
With the LOQ and the MDL, false negatives are controlled at the LOQ and false positives are controlled at the MDL

33. Reason #2 that we need MDLs
MDLs are needed in risk assessment
Handling non-detects
Substitute a value such as ½ detection limit or detection limit
More sophisticated methods such as Maximum Likelihood estimation and Regression on Order statistics
These still benefit from a detection limit as low as possible
If we do not have a detection limit, the Quantitation limit will become the new Detection limit

34. How to do a LOQ / MDL study

35. Select LOQ Choose your LOQ
Must be at or above low calibration standard
If blanks are non zero, then calculate mean + 3X standard deviation. This will approximate the MDL and spiking level should be at least 2-3 times higher
Spike ideally in the range x LOQ

36. Run the spiked and blank samples
Spikes
Minimum 7 spikes
Minimum 3 separate batches and three separate days
Prep and analytical
Minimum 2 on each instrument
Blanks
Use existing
If new method, minimum 7, at least 3 batches, at least 3 days, at least 2 per instrument

37. Initial evaluation
Do the spike results meet qualitative identification criteria in the method?
Calculate precision and accuracy, and the MDL
Adjust the LOQ if necessary

38. Good precision, good recovery
Spike 1 2 3 4 5 6 7 10
9.5
9.8
10.2
10.6
9.4
9.7
9.9
MEAN
STD. DEV
MDL S
0.4
1.3
Blanks ND
MDL B
0.0
MDL
3X MDL
LOQ
3.9
10.0
Success!
Spikes work for calculation of the MDL
And
Verification of the LOQ

39. Good precision, moderate recovery
Spike 1 2 3 4 5 6 7 10
7.3
6.9
8.1
7.7
7.9
MEAN
STD. DEV
MDL S
7.5
0.5
1.4
Blanks ND
MDL B
0.0
MDL
3X MDL
LOQ
4.3
10.0
Success!
Spikes work for calculation of the MDL
And
Verification of the LOQ

40. Poor/Moderate precision and recovery
Spike 1 2 3 4 5 6 7 10
7.3
7.6
5.7
7.2
7.9
5.3
MEAN
STD. DEV
MDL S
6.7
1.0
3.2
Blanks ND
MDL B
0.0
MDL
3X MDL
LOQ
9.7
10.0
Success!
Spikes work for calculation of the MDL
And
Verification of the LOQ

41. Poor precision, poor recovery
Spike 1 2 3 4 5 6 7 10
7.1
3.2
6.5
7.4
3.3
MEAN
STD. DEV
MDL S
5.1
1.9
6.1
Blanks ND
MDL B
0.0
MDL
3X MDL
LOQ
18.2
18.0
Marginal!
Spikes work for calculation of the MDL
And
Verification of the LOQ
But
LOQ must be elevated above
the spiking level

42. Poor precision, poor recovery
Spike at ½ desired LOQ
Spike 1 2 3 4 5 6 7
2.5
3.55
1.6
3.25
3.7
1.5
1.65
MEAN
STD. DEV
MDL S
2.54
0.97
3.04
Blanks ND
MDL B
0.0
MDL
3X MDL
LOQ
9.12 10
Success!
Spikes work for calculation of the MDL
And
Verification of the LOQ

43. Good precision, elevated blanks
Spike 1 2 3 4 5 6 7 10
13.5
12.8
14.2
14.6
13.4
13.7
13.9
MEAN
STD. DEV
MDL S
0.6
1.8
Blanks
3.1
4.2
3.9
4.4
3.8
3.2
MDL B
0.5
5.3
MDL
3X MDL
LOQ
16.0
Marginal!
Spikes work for calculation of the MDL
And
Verification of the LOQ
But
LOQ must be elevated above
the spiking level

44. Determine the LOQ – with 10% RSD
Spike at:
If RSD is 10%, the standard deviation is:
So MDL would be about: 3
CHECK: Is spike concentration at least 3x MDL?
YES: MDL (3) x3 = 9, and 10 is greater than 9.
Spike conc. 10 c
Standard Deviation=1
MDL

45. Determine the LOQ – with 20% RSD
Spike at:
If RSD is 20%, the standard deviation is:
So MDL would be about: 6
CHECK: Is spike concentration at least 3x MDL?
NO: MDL (6) x3 = 18. Ten is not greater than 18. LOQ needs to be at least 18.
Spike conc. 10
Standard Deviation= 2
MDL

46. 4,6-Dinitro-2-methylphenol
MDL
100% Recovery

47. What do we expect if the true value is at the LOQ?
Known precision?
Known accuracy?
Ability to detect and report?
Freedom from false negatives?

48. What do we expect from a true value at the MDL?
Known accuracy? Ability to detect and report? Freedom from false negatives?
We do expect freedom from false positives (99%) when the analyte is not present

49. What does this mean to labs?
Clear requirements
Sensible MDLs
Level playing field
Low transition costs since existing data can be used
Note – labs should start complying with 3 batch rule right now
Some additional organizational requirements

50. What does this mean to data users?
MDLs that make sense
Much lower rate of false positives, especially for ICP, ICPMS and some general chemistry tests
Easier to compare labs
In general, more reliable data = better decision making

51. How much will MDLs change?
Analytes with minimal or no detects in blanks, eg most GC/MS analytes at normal levels:
Not Much
Analytes with frequent detects in blanks, eg, metals, very low level PAH, some general chemistry tests:
Depends
If the lab is currently adjusting MDLs to avoid excessive false positives, not much
If the lab has been pushing MDLs below levels justified by the blanks, potentially quite a bit

52. Questions?