1、Designation: E 2253 08Standard Test Method forEnthalpy Measurement Validation of Differential ScanningCalorimeters1This standard is issued under the fixed designation E 2253; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year
2、 of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon () indicates an editorial change since the last revision or reapproval.1. Scope1.1 This test method provides procedures for validatingenthalpic measurements of differential scanning calorimeters(DS
3、C) and analytical methods based upon the measurement ofenthalpy or heat by DSC. Performance parameters determinedinclude calorimetric repeatability (precision), detection limit,quantitation limit, linearity and bias. This test method isapplicable to both exothermic and endothermic events.1.2 Validat
4、ion of apparatus performance and analyticalmethods is requested or required for quality initiatives or whereresults may be used for legal purposes.1.3 The values stated in SI units are to be regarded asstandard. No other units of measurement are included in thisstandard.1.4 This standard does not pu
5、rport to address all of thesafety concerns, if any, associated with its use. It is theresponsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2E
6、 177 Practice for Use of the Terms Precision and Bias inASTM Test MethodsE 473 Terminology Relating to Thermal Analysis and Rhe-ologyE 967 Test Method for Temperature Calibration of Differ-ential Scanning Calorimeters and Differential ThermalAnalyzersE 968 Practice for Heat Flow Calibration of Diffe
7、rentialScanning CalorimetersE 1142 Terminology Relating to Thermophysical PropertiesE 1860 Test Method for Elapsed Time Calibration of Ther-mal AnalyzersE 1970 Practice for Statistical Treatment of Thermoanalyti-cal DataE 2161 Terminology Relating to Performance Validation inThermal Analysis2.2 Othe
8、r Standard:United States Food and Drug Administration, Q2B Valida-tion of Analytical Procedures: Methodology, 62 FR27464, May 19, 199733. Terminology3.1 Technical terms used in this test method are defined inPractice E 177 and in Terminologies E 473, E 1142, andE 2161, including analyte, detection l
9、imit, differential scanningcalorimetry, enthalpy, extrapolated onset value (temperature),linearity, mean, precision, quantitation limit, relative standarddeviation, repeatability, standard deviation, thermal curve andvalidation.4. Summary of Test Method4.1 Temperature and time are the primary indepe
10、ndentparameters and heat flow is the primary dependent experimen-tal parameter provided by DSC. Integration of heat flow, as afunction of time, yields enthalpy (heat).4.1.1 Time, measured by the DSC apparatus, shall conformto better than 0.1 % verified by Test Method E 1860 andreported.4.1.2 Heat fl
11、ow, a measured value, is validated by itsintegration over time to obtain the desired calorimetric (enthal-pic) information of interest. Determination and verification ofenthalpy is the primary scope of this test method.4.2 Calorimetric validation of a differential scanning calo-rimetric apparatus at
12、 a single temperature is performed usingthe indium metal melt as an analyte.4.3 Validation of a DSC method based upon enthalpicmeasurement may be performed using the test specimen as theanalyte.4.4 The enthalpy of three (or more) specimens (nominallyrepresenting the maximum, midpoint and minimum of
13、therange of the test method) are measured in triplicate (or more).A fourth blank specimen, containing no analyte, is alsomeasured in triplicate.1This test method is under the jurisdiction ofASTM Committee E37 on ThermalMeasurements and is the direct responsibility of Subcommittee E37.01 on ThermalTe
14、st Methods and Practices.Current edition approved Sept. 1, 2008. Published October 2008. Originallyapproved in 2003. Last previous edition approved in 2003 as E 225303.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at serviceastm.org. For Annual
15、 Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.3Available from FDA, 5600 Fishers Lane, Rockville, MD 20857.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.NOTE 1Repeatabilit
16、y is determined by performing a sufficient num-ber of determinations to calculate statistically valid estimates of thestandard deviation or relative standard deviation of the measurement.4.4.1 Calorimetric linearity and bias are determined fromthe best-fit straight-line correlation of the results fr
17、om mea-surements of the three (or more) specimens.4.4.2 Calorimetric detection limit and quantitation limit aredetermined from the standard deviation of the blank determi-nation.4.4.3 Calorimetric repeatability is determined from the re-peatability measurement of the three (or more) specimens.5. Sig
18、nificance and Use5.1 This test method may be used to determine and validatethe performance of a particular DSC apparatus.5.2 This test method may be used to determine and validatethe performance of a particular method based upon a DSCenthalpic measurement.5.3 This test method may be used to determin
19、e the repeat-ability of a particular apparatus, operator or laboratory.5.4 This test method may be used for specification andregulatory compliance purposes.6. Apparatus6.1 Differential Scanning CalorimeterThe essential in-strumentation required to provide the minimum differentialscanning calorimetri
20、c capability for this test method include:6.1.1 DSC Test Chamber, composed of:6.1.1.1 Furnace(s), to provide uniform controlled heating orcooling of a specimen and reference to a constant temperatureor at a constant rate within the applicable temperature range ofthe test method.6.1.1.2 Temperature S
21、ensor, to provide an indication of thespecimen temperature to readability required.6.1.1.3 Differential Sensor, to detect a heat flow differencebetween the specimen and reference.6.1.1.4 A means of sustaining a test chamber environmentof an inert purge gas at a rate of 10 to 50 mL/min 6 10 %.NOTE 2T
22、ypically, 99+ % pure nitrogen (or other inert gas, such asargon or helium) is employed when oxidation in air is a concern. Unlessthe effects of moisture are to be studied, the use of a dry purge gas isrecommended, especially for operation at subambient temperatures.6.1.2 Temperature Controller, capa
23、ble of executing a spe-cific temperature program by operating the furnace(s) betweenselected temperature limits at a rate of temperature changeconstant to 6 1 % or at an isothermal temperature constant to6 0.5 C.6.1.3 Data Collection Device, to provide a means of acquir-ing, storing, and displaying
24、measured or calculated signals, orboth. The minimum output signals required for differentialscanning calorimetry are heat flow, temperature, and time.6.1.4 Containers, (pans, crucibles, vials, lids, closures,seals, etc.) that are inert to the specimen and referencematerials and that are of suitable
25、structural shape and integrityto contain the specimen and reference in accordance with thespecific requirements of the test method.6.2 Balance, of 100 mg or greater capacity to weighspecimens and containers to 6 1 g.NOTE 3A balance of this high precision is required so that weighingimprecision is no
26、t part of the overall method imprecision.7. Reagents and Materials7.1 Indium Metal, 99.99+ % purity, preferably a certifiedreference material for which the melting temperature andenthalpy of fusion are known.8. Calibration and Standardization8.1 After turning the power on, allow the instrument toequ
27、ilibrate for at least one hour prior to any measurements.8.2 Perform any cleaning and calibration procedures de-scribed by the manufacturer in the apparatus OperatorsManual.8.3 If not previously established, perform temperature andheat flow calibrations according to Practices E 967 and E 968respecti
28、vely, using the same purge gas, purge gas flow rate andheating rate (here 10 C/min) to be used for validationexperiments.8.4 If not previously established, obtain the instrumentselapsed time conformance using Test Method E 1860.9. Procedure for Determining Calorimetric Repeatability,Detection Limit,
29、 Quantitation Limit, Linearity, andBias9.1 This process involves characterizing, in triplicate, ablank and three (or more) test specimens taken to represent thelow, medium and high extremes of the range over whichperformance is to be validated.NOTE 4The details of this procedure are written using in
30、dium as ananalyte. For validation of an enthalpic method, test specimens represent-ing the range of that method shall be used, and steps 9.2 to 9.7 replacedwith the enthalpic method procedure.9.2 Prepare three (or more) indium test specimens coveringthe enthalpy or mass range of the tests. Nominal m
31、ass valuesmight be 1, 10, and 20 mg. Measure the mass of each of thesespecimens to the nearest 1 g and record as Mmin, Mmid, andMmax. Enclose each test specimen within clean specimencontainers and lids. Also prepare a blank specimen thatcontains no analyte but otherwise is similar to the specimenspr
32、epared above.NOTE 5Most thermoanalytical methods cover 1.5 to 2 decades ofrange. The mass values selected should be approximately equally distrib-uted over the anticipated range. Other masses and mass ranges may beused but shall be reported.9.3 Load the largest specimen into the instrument chamber,p
33、urge the chamber with dry nitrogen (or other inert gas) at aflow rate of 10 to 50 mL/min 6 10 % throughout theexperiment. An empty sample specimen container is loaded inthe reference position.9.4 Erase any thermal history in the test specimen byheating the specimen to 180 C, then cool at 5 C/min to
34、120C. The thermal curve need not be recorded.9.5 Equilibrate at 120 C for one minute.9.6 Heat the test specimen at 10 C/min through the indiummelting transition to 180 C and record the thermal curve.NOTE 6Other heating rates may be used but shall be reported.E22530829.7 Cool the test specimen to 120
35、 C at 5 C/min, then coolto ambient temperature at any convenient rate. The thermalcurve need not be recorded.9.8 Construct a baseline for the melting endotherm byselecting a point on the curve immediately before and anotherimmediately after the endotherm. Record the temperatures ofthese two points a
36、s T1and T2. Construct a linear baselinebetween the two points (see Fig. 1).9.9 Integrate, as a function of time, the heat flow describedby the constructed baseline and the melting endotherm. Recordthis value as enthalpy (DQmax(1), in mJ).9.10 Repeat steps 9.3 through 9.9 for the medium mass testspec
37、imen from step 9.2. Use the same integration limits (T1andT2) determined in step 9.8. Record this value as enthalpy(DQmid(1) , in mJ).NOTE 7Loading and unloading of the specimen is required todetermine analytical repeatability. If only instrumental repeatability isbeing determined, the specimen may
38、be left in place between determina-tions.9.11 Repeat steps 9.3 through 9.9 for the small mass testspecimen from step 9.2. Use the same integration limits (T1andT2) determined in step 9.8. Record this value as enthalpy(DQmin(1), in mJ).9.12 Repeat steps 9.3 through 9.9 for the blank test speci-men fr
39、om step 9.2. Use the same integration limits (T1and T2)determined in step 9.8 (see Fig. 2). Record this value asenthalpy (DQo(1), in mJ).NOTE 8Observe and record the sign of the value for DQo. It may bepositive or negative.9.13 Repeat steps 9.5 through 9.9 two more times for thelarge mass specimen.
40、Remove the specimen from the DSCsample chamber and reload it between each determination.Record these values as enthalpy (DQmax(2) and DQmax(3), inmJ).9.14 Repeat steps 9.5 through 9.9 two more times for themedium mass specimen. Remove the specimen from the DSCsample chamber and reload it between eac
41、h determination.Record these values as enthalpy (DQmid(2) and DQmid(3), inmJ).9.15 Repeat steps 9.5 through 9.9 two more times for thelow mass specimen. Remove the specimen from the DSCsample chamber and reload it between each determination.Record these values as enthalpy (DQmin(2) and DQmin(3), inm
42、J).9.16 Repeat steps 9.5 through 9.9 two more times for theblank specimen. Remove the specimen from the DSC samplechamber and reload it between each determination. Recordthese values as enthalpy (DQo(2) and DQo(3), in mJ).9.17 Calculate the mean (Q), standard deviation (s) andrelative standard devia
43、tion (RSD) for the enthalpy from thereplicate determinations made on each of the three massspecimens (see Practice E 1970). Record these values as Qmax,Qmid, Qmin, smax, smid, smin, and RSDmax, RSDmid, and RSDmin,respectively. Calculate the mean and standard deviation for theenthalpy determination o
44、f the blank. Record these values as Qoand sorespectively.9.18 Using the standard deviation for the enthalpy of theblank (so) from step 9.17, determine the instrument detectionlimit (DL) and quantitation limit (QL) as in calculations 10.2and 10.3. Report DL and QL.9.19 Calculate the pooled relative s
45、tandard deviation for theenthalpy of fusion from the RSDmax, RSDmid, and RSDmin,obtained in step 9.17 (see Practice E 1970). Report this valueas the Calorimetric Repeatability value (r).9.20 Using the three (or more) mass values from step 9.2 asthe independent (X) values and the three (or more) mean
46、enthalpy values from step 9.17 as the dependent (Y) values,determine the least square best fit values for the slope (m)inmJmg-1, and intercept (b) in mJ (see Practice E 1970).FIG. 1 Integration of Large Indium Melting EndothermE2253083NOTE 9The units of mJ mg-1for slope are equivalent to the units o
47、fJg-1.9.21 Calculate the Percent Linearity (L) of the enthalpy offusion data from the values in step 9.20 and the calculation of10.4.9.22 Compare the slope (mean enthalpy of fusion) from step9.20 to the accepted reference value for enthalpy of fusion asin calculation of 10.5 (see Practice E 968). Re
48、port this value asthe Calorimetric Bias (Bias) as a percentage.10. Calculations10.1 When performing these calculations, retain all avail-able decimal places in the measured values and in intermediatecalculated values. The final result should be rounded to threesignificant figures.10.2 Detection Limi
49、t (DL) is given by:DL 5 3.3 so(1)where:DL = detection limit, mJ, andso= blank enthalpy standard deviation, mJ.NOTE 10To express the Detection Limit in terms of mass of analyte,the value for DL may be divided by the slope value m from 9.20.10.3 Quantitation Limit (QL) is given by:QL 5 10 so(2)where:QL = quantitation limit, mJ.NOTE 11To express the Quantitation Limit in terms of mass of theanalyte, the value for QL may be divided by the slope value m from 9.20.10.4 Percent Linearity (L) is given by:L 5F100 % 3 ? Largest dY ?!m 3 Mmax1 bG(3)where:L = linearity
