NF Ethylcellulose Assay Procedure

Transcription

1 The Dw Chemical Cmpany September 2, 2011 NF Ethylcellulse Assay Prcedure Purpse This dcument is written t prvide guidance fr analysts cnducting the NF Ethylcellulse assay test methd. The prcedure utlined in this dcument is based n the prcedure prvided in the current NF mngraph and includes additinal guidance and ntes as a reference t the analyst. It is based n the mngraph test prvided in versin USP 34/NF 29. Safety Each analyst shuld be acquainted with ptential hazards f the reagents, prducts, and slvents befre beginning labratry wrk. SOURCES OF INFORMATION INCLUDE: MATERIAL SAFETY DATA SHEETS, LITERATURE, AND OTHER RELATED DATA. Safety infrmatin n nn-dw prducts shuld be requested frm the supplier. Dispsal f reagents, reactants, and slvents must cmply with lcal, state, and federal laws and regulatins. Hydridic acid and its reactin byprducts are highly txic. Perfrm all steps f the assay preparatin and the standard preparatin in a prperly-functining hd. Specific safety practices t be fllwed are t be identified and fllwed by the analyst perfrming this test. Review the Material Safety Data Sheet (MSDS) fr this material prir t wrking with this chemical. Persnal prtective equipment t be wrn during the prcedure includes chemical gggles and acidresistant glves. If the glves becme cntaminated, dispse f them immediately. All wrk with hydridic acid must be dne in a fume hd and all samples shuld be stred in the hd. During the reactin, the glass vials are under pressure at high temperature. Exercise cautin in handling the vials and cnduct the reactin and agitatin behind a safety shield and in a fume hd. Assay Prcedure Hydridic Acid The NF assay prcedure des nt prvide specifics regarding this reagent. Dw recmmends use f stabilized 57% hydridic acid. Use f hydridic acid cntaining <55% cncentratin has been identified as a rt cause fr lwer than expected results. Use f 57% hydridic acid is recmmended (this is the highest purity available n the market). Use f nn-stabilized hydridic acid ver 6 mnths ld has been identified as a rt cause fr lwer than expected results. Dw uses HI stabilized with hypphsphrus acid within 3 mnths f pening the bttle. Strage cnditins prvided by the supplier are recmmended.

2 Internal Standard Slutin Dilute 120 µl f tluene with -xylene t 10 ml. Standard Slutin Transfer mg f adipic acid, 4.0 ml f the Internal standard slutin and 4.0 ml f hydridic acid int a suitable 10-mL thick-walled reactin vial with a pressure-tight septum clsure. Clse the vial tightly, and weigh the vial and cntents accurately. Afterwards inject 50 µl f idethane thrugh the septum with a syringe, weigh the vial again, and calculate the mass f idethane added, by difference. Shake well, and allw the layers t separate. Use the upper layer fr analysis. It is suggested that the exact purity f the idethane be btained frm a supplier Certificate f Analysis r via analytical testing and used when calculating the amunt f idide in the standard preparatin. Failure t crrect the mass fr the purity f the standard will cause lwer assay results t be btained. Care must be taken t ensure the purity f the adipic acid. If it is cntaminated with trace levels f Ethylcellulse, the final result culd be higher than expected. Sample Slutin Transfer 50.0 mg f Ethylcellulse, 50 mg f adipic acid, and 2.0 ml f the Internal standard slutin int a suitable 5-mL thick-walled reactin vial with a pressure-tight septum clsure. Cautiusly add 2.0 ml f hydridic acid, immediately clse the vial tightly, and weigh the cntents and the vial accurately. Shake the vial fr 30 s, heat t 125 fr 10 min, allw t cl fr 2 min, shake again fr 30 s, and heat t 125º fr 10 min. Afterwards allw t cl fr 2 min, and repeat shaking and heating fr a third time. Allw the vial t cl fr 45 min, and re-weigh. If the lss is greater than 10 mg, discard the mixture and prepare anther. Use the upper layer fr analysis. Vial Dw uses a 5-mL pressure-tight serum vial, 40-mm in height, 20-mm in utside diameter, and 13- mm in inside diameter at the muth. The vial is equipped with a pressure-tight septum having a plytetraflurethylene (PTFE)-faced butyl rubber and an air-tight seal using an aluminum crimp sealing system fr air-tightness. Accurate Weighing A 5-place balance is suggested (weighing t the nearest g). Care must be taken t ensure stable accurate weight readings are btained. Factrs t cnsider and eliminate/minimize include air currents, static charge, and humidity (misture pick-up). Care needs t be taken t cmplete the assay preparatin steps in such a way that misture is nt added t the cntents f the vial. Quick and careful weighing with capping f the vial in between additins is suggested. Derivatizatin Reactin This is a very critical step in the assay testing and has multiple surces f ptential rt causes fr unexpected results. The NF assay prcedure des nt specify hw t heat the sample slutins. At Dw, the reactin step is carried ut using an electrically-heated, thermstat-cntrlled, insulated, aluminum blck with an aluminum lid designed t fully cver the vials during the mixing step. This heating blck is munted n a hrizntal linear shaker with a prgrammable strke rate. The blck has 8 wells machined t clse tlerance t ensure cnsistent heating in all 8 wells. The cntents in the vial must be cmpletely within the wells f the heating unit during the heating step. A cver ver the wells hlding the vials is als recmmended t better ensure unifrm heating f the entire cntents and headspace f the sealed vials. If multiple vials are heated at the same time, it is imprtant t ensure that the heating prfile fr the heating element is cnsistent frm vial t vial. This has been identified as a rt cause fr incnsistent and lwer than expected results.

3 Temperature f the sample slutin is critical. As stated in the mngraph, the cntents f the vial are t be heated t 125º fr 10 min. It is imprtant t ensure the sample slutin reaches the target temperature quickly s that the reactin is cnducted cnsistently and cmpletely each time. At Dw, the vials are heated t 125 ± 2 ºC fr the specified heating times. Take care when mixing the cntents f the vial by hand prir t placing in the heater. The reagents and sample in the vial are nt sluble at rm temperature and can adhere t the sides f the vial. This culd lead t ineffective heating and derivatizatin f the ethylcellulse pwder resulting in lwer than expected results. This is a leading surce f variability in the measurement. Fr safety, it is strngly suggested that a reciprcal shaker r magnetic stirrer be used during the shaking steps f the reactin. Shaking the vials by hand intrduces a pssible safety risk (thermal r chemical expsure due t ver-pressurizatin f the vials during the reactin). Mixing must be as cntinuus and vigrus as pssible t ensure cmplete derivatizatin. With a linear shaker, it is suggested that at least 100 strkes per minute (clser t 200 strkes per minute is recmmended) be used t ensure cmplete derivatizatin. Chrmatgraphic System Mde: GC Detectr: Flame inizatin Clumn: 2-mm 5.0-m stainless steel clumn packed with 3% G2 n µm mesh supprt S1A Temperature Clumn: 80 Injectr: 200 Detectr: 200 Carrier gas: Nitrgen Flw rate: 15 ml/min Injectin vlume: 1 µl Cnditining f the packed clumn is recmmended prir t initial use t ensure stability during sample analysis. At Dw, this is accmplished by the fllwing thermal and chemical cnditining prcedures: Thermal Cnditining After the clumn is first installed, heat t 200 C at rate f 2 C per minute and hld fr apprximately 16 hurs (r vernight). It is critical that the clumn nt be expsed t any air during this thermal cnditining. Return the ven and clumn t the nrmal analysis temperature f 80 C. Chemical Cnditining If the clumn has been repacked, make three separate 5-L injectins f the pure idethane standard. If the clumn has been replaced, make five separate 5-L injectins f the pure idethane standard. Prepare a Reference Slutin and inject 2-L a minimum f 20 times until the respnse factrs are stabilized within 5% relative. Run a blank t generate a baseline. If the baseline is flat, inject a reference standard and cmpare results t previus trend charts t supprt integrity f the system. It is recmmended that the GC packed clumn be replaced at least annually, mre ften if system suitability r ther trending results indicate clumn degradatin. If samples are analyzed infrequently, it is recmmended that injectin f a previusly-prepared sample slutin be cnducted t cnditin the clumn. The results frm this analysis shuld nt be used fr quantitative purpses.

4 At Dw, helium is used as the carrier gas (instead f nitrgen). It is recmmended that the carrier gas be passed thrugh xygen and misture traps t better ensure clumn integrity and lngevity. The mngraph calls fr the temperature f the clumn t be maintained at 80 C. Dw fllws the elutin with a temperature ramp t remve any residue frm the clumn. The recmmended temperature prgram: Oven temperature: 80 C hld fr 15 minutes, ramp t 200 C and hld fr 15 minutes Fr custmers wh d nt have access t a packed clumn GC system, equivalent results can be btained using a capillary clumn such as Phenmenex ZB-5, 30 m x 0.53 mm x 5.0 micrn film thickness in a split mde with a split rati f 5:1. System suitability Sample: Standard Slutin [Nte - The relative retentin times fr idethane, tluene, and 0-xylene are 0.6, 1.0, and 2.3 respectively.] Suitability requirements Reslutin NLT 2.0 between idethane and tluene Analysis f the upper layer can be cnducted using manual r autmated injectins. If autmated injectins are used, transfer f an aliqut f the upper layer t an autsampler vial is required. Care must be taken during this transfer t prevent vaprizatin f the slvent as this culd lead t higher than expected results. At Dw, small vlume inserts are used with the autsampler vials. Transfer f the sample slutin is cnducted in a single step using a syringe and the autsampler vial is immediately crimped shut. At Dw, testing is cnducted rutinely. A reference Ethylcellulse material is analyzed with each set f samples t demnstrate cnsistency f the entire system (sample preparatin, derivatizatin, and analysis). Trending f the results is mnitred t ensure the system is in cntrl. Analysis Samples: Standard slutin and Sample slutin Calculate the percentage f ethxy cntent f the Ethylcellulse as declared in the labeling: Result = (451,000/312) (R U m 2 )/[(R S m 1 ) (100-d)] R U = rati f the idethane peak area t the tluene peak area frm the Sample slutin m 2 = mass f idethane used in the Standard slutin (mg) R S = rati f the idethane peak area t the tluene peak area frm the Standard slutin m 1 = mass f Ethylcellulse used in the Sample slutin (mg) d = lss n drying as a percentage Acceptance criteria: % n the dried basis

5 Our experience has shwn that there are many ways t get lwer than expected results. Careful attentin must be paid t all aspects f this prcedure t ensure cnsistent and accurate results. Please cntact me with any questins regarding this test prcedure. Sincerely, Barbara Serr Business Analytical Leader Dw Specialty Materials 2301 N. Brazsprt Blvd. B-1216 Freeprt, TX USA Phne: (979) brserr@dw.cm