欧盟OMCL仪器确认附件1HPLC确认Word格式文档下载.docx
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欧盟OMCL仪器确认附件1HPLC确认Word格式文档下载.docx
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Parametertobechecked需检查的参数Flowrate流速Proportioningaccuracyprecision(gradienttest)配比准确度和精密度(梯度测试)?
Proportioningripple配比波动Carry-over残留accuracy?
?
and?
TypicaltoleranceLimits典型允差限度±
5%±
2≤0.2%RSD≤1.0%seeAnnexI见附件1±
3°
C±
2°
Cr2≥0.999±
2nm±
3nm±
seeAnnexIseeAnnexI见附件1seeAnnexI见附件1seeAnnexI见附件10.1mV/minseeAnnexI见附件1seeAnnexI见附件1seeAnnexI见附件1r&
gt;
0.999Injector进样器Autosampler自动进样器Ovenorcoolingdevice柱温箱或冷却装置UV/DADdetectorUV/DAD检测器Fluorescencedetector荧光检测器?
Volumeprecision进样量精密度?
Thermostattingprecision恒温准确度和精密度Thermostattingaccuracy恒温准确度?
Linearity线性度Wavelengthaccuracyexcitation?
波长激发准确度Wavelengthaccuracyemission?
波长发射准确度Sensitivity灵敏度度?
Stabilityofthesignal信号稳定?
性Signal/Noiseratio信噪比Driftovertime飘移Signal/Noiseratio信噪比Sensitivity灵敏度Driftovertime飘移Linearity线性?
Wavelengthaccuracy波长准确?
Electrochemicaldetector?
电化学检测器Accuracyofthesignal信号准确?
RIDdetectorRID检测器CDdetectorCD检测器?
TABLEIV表四LevelIV.In-useinstrumentchecks第四级在用仪器检查ExamplesofrequirementsforHPLCinstrumentswithUVorDADdetectors配备UV或DAD检测器的HPLC仪器的要求举例
BEIJINGGELEGSCI.-TECH.CO.LTDParametertobechecked需检查参数?
TypicaltoleranceLimits限度SystemsuitabilitycheckfortheMethod方AccordingtoPh.Eur.orMAHdossieror法系统适用性检查validatedin-houseMethod根据欧洲药典或MAH文件或公司内部经过验证的方法?
Peakareaprecision(applicabletotheRSD≤1.5%mainpeaksinthetestsolution)(unlessotherwiseprescribedinthesystemoftheMethod,e.g.specificrequirementsfromPh.Eur.2.2.46,APImonographsorMAdossiers)除非在方法的系统适用性里有描述,例如EP2.2.46特定要求,原料药各论或MA文件峰面积准确度(适用于供试液中主峰面积)suitability?
Retentiontimeprecision保留时间精密度RSD±
5%Carry-over(bycomparingconsecutive≤0.2%standard(ofthesubstancebeingquantified)andblankinjections)残留(通过比较连续(进行定量检测的物质)标准和空白进样)?
Signal/Noiseratio(tobeappliedforAccordingtoPh.Eur.relatedsubstancestest)信噪比(用于有关物质检测)ANNEXI附件1LevelIII.Periodicandmotivatedinstrumentchecks第三级定期性的主动仪器检查根据欧洲药典ThisAnnexcontainspracticalexamplesoftestsandtheirassociatedtoleranceLimitsforseveralparametersrelatedtotheperformanceofthedifferentmodulesofaHPLC.本附件包括一些实用几个与HPLC不同模块相关的参数检测举例及其相应的可接受限度。
TheseexamplescanbeconsideredbytheOMCLsaspossibleapproachestoperformtheLevelIIIoftheequipmentqualificationprocess:
“Periodicandmotivatedinstrumentchecks”.这些例子可以认为是OMCL实验室可能的进行第三级仪器确认的方法“周期主动仪器检查”HPLCSOLVENTDELIVERYSYSTEM高压液相溶剂传输系统ThefollowingtestsareproposedfortheperiodicandmotivatedcheckoftheHPLCsolventdeliverysystem:
flowrateandgradienttest.以下测试作为HPLC溶剂传输系统周期性主动检查:
流速和梯度检查FLOWRATE流速
BEIJINGGELEGSCI.-TECH.CO.LTDMaterials:
材料Volumetricflaskof5or10ml5ml或10ml的容量瓶Calibratedchronometer校正过的计时计Settings:
设置Mobilephase:
degassedwater流动相:
脱过气的水Nocolumn(openend)*无柱(开放式)*Flowrate:
adjustedbetween0.5and3.0ml/min流速:
调节在0.5到3.0ml/minIfhigh-pressuremixingsystemsareinstalled,thistesthastobedoneoneachsolventchannel.如果有安装高压混合系统,本测试应在每一溶剂通道进行。
Forcertainequipment,e.g.inthecaseoflowflowrates,thecheckwouldbeperformedbyusingacolumnorabackpressureregulator.对于一定的仪器,例如,流速较低时,采用一根柱子或背压调整器进行检查Method方法:
Settheflowrateatanappropriatelevelandmeasurethetimeneededtofillthevolumetricflaskuptothemark.Recordthetimeneeded.将流速设定在一个合适的水平,测量将容量瓶装满至刻度的时间。
记录所用的时间。
f=V/tf=(V×
60)/tf.................measuredflowrate[ml/min]测量的流速t.................elapsedtimetofilluptomark[s]充满至刻度所花的时间V...............volumeofthevolumetricflask[ml]容量瓶的体积D=100×
(f-F)/FD...............deviation[%]偏差F...............adjustedflowrate[ml/min]调节后的流速f.................measuredflowrate[ml/min]测量的流速
BEIJINGGELEGSCI.-TECH.CO.LTDLimits限度:
±
5%GRADIENTCOMPOSITIONANDRIPPLE梯度组成和波动Settings:
设置Stainlesssteelcapillarye.g.2000x0.12mminstalledinsteadofacolumn不锈钢毛细管,例如2000X0.12mm,代替色谱柱安装于仪器Detection:
UV-Detectoradjustedto265nm检测器:
紫外检测器调节至265nmMobilephaseA:
degassedwater流动相A:
脱气水MobilephaseB:
degassedwatercontaining0.5%acetone流动相B:
含0.5%的脱气水Flowrate:
1.0ml/min流速:
1.0ml/分钟Method方法:
Thetestiscarriedoutinthefollowingwaybyusingagradientprogramdependingonthenumberofsolventchannelsandtheconfigurationofthesystem:
按下列方法进行测试,根据通道数量不同使用下列不同系统参数和梯度进行洗脱A-BA-BandA-CA-C,A-BandB-Dtime[min]时间[分钟]0.00.11010.12020.13030.14040.1%mobilephaseA(water)%流动相A(水相)10090905050101000100%mobilephaseB01010505090901001000%流动相B(water-acetonemixture)(水-丙酮混合物)
BEIJINGGELEGSCI.-TECH.CO.LTDStartthetestbypumpingwaterforatleast10mintoequilibratethesystem.开始测试前,先用水平衡系统至少10分钟。
Thezero%valueatthestartofthetestisthebaseline.Allstepsaremeasuredatthebeginningofthehorizontalpartofthelineeitherbysoftwareormanuallyonthepaperprintusingaliner.Theheightofthe100%water/acetonemixtureisusedasthe100%valueinthefollowingcalculation.开始时的0%值是基线值。
所有步骤均在开始时测量基线的水平部分,由软件或手动在纸上用衬垫打印。
100%水/丙酮混合物的高度在以下计算中作为100%值。
%H=100*h/H%H............calculatedcomposition计算组成h................heightofthemeasuredline测量线的高度H...............heightofthe100%water/acetonemixtureline(mobilephaseB)100%水/丙酮混合物线的高度(流动相B)d=%H-Gd................deviation偏差G...............gradientcompositionadjusted[%acetone/watersolutionmixture=mobilephaseB]梯度组成调节【%丙酮/水溶液混合物=流动相B】Limits限度:
Absolutedeviation:
2oftheadjustedvalue绝对偏差:
调整值的±
2Therippleofthegradientcompositionisthepercentageofnoiseofthe50%linefromthegradientprogram.梯度组分的波动为梯度程序噪声基线的50%%R=100*N/h50%R............ripple波纹h50.............heightofthe50%line50%的线高度N...............heightofthenoiseline,measuredduring1minuteinthelinearregion噪声线高度,在线性区域1分钟测量的结果Limit限度s:
≤0.2%HPLCINJECTOR进样器Volumeprecisionandcarry-overarethetestsproposedfortheperiodicandmotivatedcheckoftheHPLCinjector.建议在HPLC进样器周期性主动检查中进行体积精密度和残留检查
BEIJINGGELEGSCI.-TECH.CO.LTDVOLUMEPRECISIONANDCARRY-OVER体积精密度和残留Solutions:
溶液SolventA:
methanol:
waterR,60:
40.溶液A:
乙醇:
水(试剂)=60:
40Referencesolution(a):
dissolve15.0mgmethyl-,ethyl-,andpropylparabenein100.0mlofsolventA.对照液(a):
取15.0mg乙基、甲基和尼泊金丙酯溶于100.0ml溶剂A中Referencesolution(b):
Dilute1.0mlofreferencesolution(a)to10.0mlofsolventA.对照液(b):
取1.0ml对照液(a)用溶于10.0ml溶剂A中Referencesolution(c):
Dilute1.0mlofreferencesolution(b)to100.0mlofsolventA.对照液(c):
取1.0ml对照液(b)用溶于100.0ml溶剂A中Settings:
设置Column:
Lichrospher100RP8,5um,125x4mm,withoutprecolumn色谱柱:
Lichrospher100RP8,5um,125x4mm,无衬管Mobilephase:
water=60:
40流动相:
水=60:
40Flowrate:
1.0ml/min流动速度:
1.0ml/分钟Detection:
254nm检测器:
254nmInjectionvolume:
20μl进样体积:
20ulMethod方法:
Injectionscheme:
进样序列———6xreferencesolution(b)对照液(b)6针1xreferencesolution(a)对照液(a)1针1xsolventA(blankinjection1)溶剂A(空白)1针
BEIJINGGELEGSCI.-TECH.CO.LTD———1xreferencesolution(b)对照液(b)1针1xsolventA(blankinjection2)溶剂A(空白2)1针1xreferencesolution(c)对照液(c)1针Limit
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