Ning Chang PhD, Isil Dilek PhD, Bryan Dockery, Kevin Gates, Huahua Jian PhD, Mitzi Rettinger, Krystal Silva, Uma Sreenivasan PhD
Ethanol standards are widely used in forensic and toxicology applications for determination of blood alcohol content. Results of blood alcohol testing have significant legal implications and are frequently used as evidence in courts of law. The blood alcohol analysis process must therefore be reliable and defensible. A critical component of blood alcohol analysis is the calibrator used for quantitation of results. Ethanol reference standards are widely available for this purpose and are sold in many formats – bottled and ampouled. The accuracy and uncertainty associated with these standards are important contributors to the accuracy and associated uncertainty of the blood alcohol test result. It is imperative that the uncertainty of the reference standards be within the margins of the blood alcohol testing uncertainty and that the certified concentration is accurate and completely traceable to international units of measure. Cerilliant Certified Ethanol Reference Standards are manufactured and certified to ISO Guide 34 and ISO/IEC 17025 standards and are traceable to SI units and to NIST SRM ethanol standards. The preparation, certification and uncertainty of these standards is presented in this poster.
Complete & accurate characterization of the neat ethanol is essential to accuracy of the solution
Uncertainty of residual water content is based on repeatability experiments using the Karl Fischer Coulometric method (USP<921>).
Results were combined in a Kratgen Spreadsheet1 to determine uncertainty of the neat ethanol purity factor
PurityFactor = (100 -(wt%H2O))(ChromPurity/100)±U
All instruments are fully qualified and calibrated.
Requalification is performed annually and system suitability is performed daily.
Balances are qualified and calibrated. All weighings are traceable to SI units.
Mass measurement uncertainty was determined from a combination of balance manufacturer specified tolerances for sensitivity and linearity and repeatability experiments following specified weighing procedures. Balance manufacturer tolerances alone are insufficient. Values are proportional to the net mass being measured and are specific to the balance utilized.
usens-Uncertainty due to the balances sensitivity tolerance
ulin-Uncertainty due to non-linearity of the characteristic curve
Thermal expansion will affect volumetric accuracy of calibrated flasks
Cerilliant evaluated every step involved in the preparation of its Certified Ethanol Solution Standards and determined that the primary contributing factors impacting uncertainty were: uncertainty of the Purity Factor; Mass Measurement uncertainty and Diluent Addition uncertainty.
Measurement Equation for Concentration Uncertainty
C = Concentration of solution (mass/volume)
mv+a = mass of analyte + vial
mv = mass of empty vial
mf+s = mass of flask + solvent
mf = mass of empty flask
d = density of solution
p = purity adjustment factor for the neat material
U = the assigned combined expanded measurement uncertainty
Measurement Equation: C=(mv+a-mv)d/(mf+x-mf)p
The Kratgen Spreadsheet shows the calculation of uncertainty and contributions of each uncertainty component.
Validated Analytical Method is used to Verify Solution Concentration and Ampoule to Ampoule Consistency
Validation ensures the analytical method is accurate, robust, repeatable and reliable
Linearity ensures the analytical method is reliable for quantitation across a range of concentrations
Uncertainty assessment for concentration verification includes uncertainty related to the analytical method response and uncertainty reported on the value assigned to the NIST SRM.
Measurement equation for uncertainty of analytical concentration verification
Areastd = area response of the standard
AreaNIST = area response of the NIST SRM
CNIST = conc of the NIST SRM with stated uncertainty
Factors Impacting Uncertainty of the Analytical Verification
Traceability is the property of a measurement result whereby it can be related to stated references usually through national or international standards through an unbroken chain of comparisons all having stated uncertainties.