仪器确认-附件7-质谱仪确认-中英文.doc

OMCL Network of the Council of EuropeQUALITY MANAGEMENT DOCUMENT质量管理文件PA/PH/OMCL (10) 86 2RQUALIFICATION OF EQUIPMENT仪器确认ANNEX 7: QUALIFICATION OF MASS SPECTROMETERS附件7：质谱仪的确认Full document title and reference 文件全名和索引号Qualification of EquipmentAnnex 7: Qualification of mass spectrometersPA/PH/OMCL(10)86 2RDocument type 文件类型Guideline Legislative basis 立法基础-Date of first adoption 首次发行日期25th May 2011Date of original entry into force 首次执行日期1st July 2011Date of entry into force of revised document 修订后执行日期-Previous titles/other references 原文件名/其它索引号-Custodian Organisation 保管机构The present document was elaborated by the OMCL Network/EDQM of the Council of EuropeConcerned Network 相关网络GEONANNEX 7 OF THE OMCL NETWORK GUIDELINE“QUALIFICATION OF EQUIPMENT”OMCL网络指南“仪器确认”附件77.1: QUALIFICATION OF GAS CHROMATOGRAPHY-MASS SPECTROMETERS WITH ELECTRON IMPACT IONIZATION (GC-EI-MS) 装备电子碰撞电离的气相色谱-质谱仪的确认Introduction 介绍The present document is the first part of the 7th Annex of the core document “Qualification of Equipment”, and it should be used in combination with it when planning, performing and documenting the qualification process of GC-EI-MS. 本文件是核心文件“仪器确认”的第7个附件，在计实施和记录GC-EI-MS的确认过程中，应与核心文件结合使用。The core document contains the Introduction and general forms for Level I and II of qualification, which are common to all type of instruments. 核心文件包括了介绍和适用于所有类型仪器的第一级和第二级确认用通用表格。The present annex contains instrument-related recommendations on parameters to be checked at Level III and IV of qualification and the corresponding typical acceptance limits, as well as practical examples on the methodology that can be used to carry out these checks. 本附件包括与仪器相关的在第三级和第四级要检查的参数及其相关的典型可接受限度的推荐，以及在实施这些检查时可以采用的方法学实例。TABLE III 表3Level III. Periodic and motivated instrument checks 第三级 周期性主动仪检查Minimum requirements for GC-EI-MS (examples)GC-EI-MS最低要求（举例）Parameter to be checked要检查的参数Typical tolerance limits典型允许限度Mass accuracy 质量准确性PFTBA (FC-43) *Or internal calibration gas 或内部校正气体m/z = 690.5m/z = 2190.5m/z = 5020.5or defined masses of internal calibration gas 0.5或内校气体指定的质量0.5Linearity * 线性r2 0.995System/instrument precision * 系统/仪器精密度1.0%*) PFTBA (FC-43): Perfluoro-tributyl-amine (CAS NO.: 311-89-7) PFTBA(FC-43): 全氟三丁胺（CAS号 311-89-7）*) In case of quantification purposes, these parameters have to be checked. 如果要进行定量检测，这些参数必须要检查。TABLE IV 表四Level IV. In-use instrument checks 第四级 在用仪器的检查Requirements for GC-EI-MSGC-EI-MS的要求Parameter to be checked要检查的参数Typical tolerance limits典型允许限度As defined by the specific analysis method or according to the Ph. Eur. Or the MAH dossier(see example in Level IV. Annex II)如特定分析方法定义，或根据欧洲药典或MAH档案（见第四级附件2的举例）Identified by library or with reference standard由图谱库进行鉴别或与对照品进行对照ANNEX I 附件1Level III. Periodic and motivated instrument checks 第三级 周期性主动仪器检查This Annex contains practical examples of tests and their associated tolerance limits for several parameters related to the performance of GC-EI-MS. 本附件包括了GC-EI-MS性能相关的几个参数的测试实例及其关联的允许限度。These examples can be considered by the OMCLs as possible approaches to perform the Level III of the equipment qualification process: “Periodic and motivated instrument checks”. 这些实例可以作为OMCL在实施第三级仪器确认过程“周期性主动仪器检查”中可以采用的方法。GENERAL CONSIDERATIONS 一般考虑- GC-MS is mainly used for the identification of unknown substances or quantification of low concentrated substances where high specificity is needed. GC-MS主要用于需要较高专属性的未知物质的鉴别，或低浓度物质的定量MASS ACCURACY 质量准确度Materials: 材料PFTBA (FC-43) or internal calibration gas PFTBA(FC-43)或内部校正气体Method: 方法Internal instrument check or spectrum of PFTBA (FC-43) in full scan mode 仪器内部检查或PFTBA（FC-43）全扫描模式光谱扫描Limits: 限度m/z = 69 0.5 m/z = 219 0.5 m/z = 502 0.5 Note: the tolerance limits for mass accuracy are only valid for quadrupole and ion trap mass spectrometers. Instruments like Time-of-Flight (TOF) or hybrid instruments like quadrupole-Time-of-Flight (QTOF) have a much better mass accuracy and adequate requirements should be applied by the laboratory. 注：质量准确度的允许限度只对四级杆和离子阱质谱仪有效。其它仪器，如飞行时间质谱（TOF）或HYBRID仪器，如四级杆-飞行时间质谱（QTOF），具有更好的质量准确性，这时化验室应采用足够好的要求。LINEARITY 线性Materials: 材料Stock solutions: 1-Octanol in dichloromethane 0.2, 0.4, 0.6, 0.8, 1.0 L/mL 贮备液：0.2, 0.4, 0.6, 0.8, 1.0 L/mL正辛醇的二氯甲烷溶液 Method: 方法2 injections of each level (injection volume: 1.0 L) 每个水平2针（进样量 1.0uL）Limits: 限度r 0.995 SYSTEM/INSTRUMENT PRECISION 系统/仪器精密度Materials: 材料Stock solution: 1-Octanol in dichloromethane 1.0 L/mL 贮备液： 1.0 L/mL正辛醇的二氯甲烷溶液Method: 方法6 injections (injection volume: 1.0 L) 6针（进样量：1.0uL）Limits (minimum requirement): 限度（最低要求）RSD 10.0% (without internal standard 没有内控标准) ANNEX II 附件2Level IV. In-use instrument checks 第四级 在用仪器检查This Annex contains practical examples of tests and their associated tolerance limits for several parameters related to the performance of GC-EI-MS. 本附件包括了GC-EI-MS性能相关的几个参数的测试实例及其关联的允许限度。These examples can be considered by the OMCLs as possible approaches to perform the Level IV of the equipment qualification process: “In-use instrument checks”. 这些例子可以认为是OMCL在进行第四级仪器确认过程“在用仪器检查”中可以使用的方法。IDENTIFICATION*) 鉴别Materials: 材料Papaverine 20.0 g/mL in methanol, Caffeine 10.0 g/mL in methanol or another compound chosen according to the specific method 20.0ug/ml帕帕菲林（罂粟碱）的甲醇溶液10.0ug/ml的咖啡因甲醇溶液或另一种根据特定的方法选择的化合物Method: 方法Identification by library 由图谱库进行鉴别Limits: 限度Positive 符合*) only in case of use of library identification 仅当使用图谱库鉴别时SYSTEM/INSTRUMENT PRECISION *) 系统/仪器精密度Materials: 材料Any of the above-mentioned reference standard solutions used for the identification 任何上述用于鉴别的标准溶液Method: 方法6 injections (injection volume: 1.0 L) 6针（进样体积1.0uL）Limits (minimum requirement): 限度（最低要求）RSD 10.0% *) in case of use for quantification 如果用于定量Other tests according to the system suitability of the analysis method in use. 其它测试应根据使用的分析方法的系统适用性。7.2 QUALIFICATION OF LIQUID CHROMATOGRAPHY-MASS SPECTROMETERS (LC-MS)* 液相-质谱（LC-MS）的确认Introduction 介绍The present document is the second part of the 7th Annex of the core document “Qualification of Equipment”, and it should be used in combination with it when planning, performing and documenting the qualification process of LC-MS*. 本文件是核心文件“仪器确认”的第7个附件的第二部分，在计划、实施和记录LC-MS确认过程中应与核心文件结合使用。The core document contains the Introduction and general forms for Level I and II of qualification, which are common to all type of instruments. 核心文件包括了介绍，和对所有类型均通用的第一级和第二级确认通用表格。The present annex contains instrument-related recommendations on parameters to be checked at Level III and IV of qualification and the corresponding typical acceptance limits, as well as practical examples on the methodology that can be used to carry out these checks. 本附件包括与仪器相关参数和对应的典型可接受限度的推荐，这些参数在第三级和第四级确认中需要进行检查，以及在实施这些检查时可以使用的方法实例。* Ionisation sources include: 电离源包括ESI: Electrospray Ionisation ESI：电喷雾离子化APCI: Atmospheric Pressure Chemical Ionisation APCI: 大气压力化学电离APPI: Atmospheric Pressure Photo-Ionisation APPI：大气压力光电离TABLE III 表3Level III. Periodic and motivated instrument checks 第三级 周期性主动仪器检查Minimum requirements for LC-MS (examples)LC-MS的最低要求（举例）For positive mode: 正模式Parameter to be checked要检查的参数Typical tolerance limits典型允许限度Mass accuracy 质量准确度Reserpine 拉舍平m/z = 609 0.5Fragmentation of m/z = 609 without fragmentation energy*无碎片能量 m/z = 609 0.5Fragmentation of m/z = 609 with fragmentation energy*有碎片能量 m/z = 448 0.5(most intense fragment)（最密碎片）* only for instruments with MS/MS capabilities.仅适用于MS/MS仪器Parameter to be checked需要检查的参数Typical tolerance limits典型允许限度Mass accuracy 质量准确度Acid Red 4 * 酸性红4号m/z = 357 0.5Fragmentation of m/z = 357 without fragmentation energy *m/z = 357无碎片能量m/z = 357 0.5Fragmentation of m/z = 357 with fragmentation energy *m/z = 357有碎片能量m/z = 170 0.5（most intense fragment）* only for instruments with MS/MS capabilities 仅适用于MS/MS仪器* Acid Red 4, CAS NO.: 5858-39-9 酸性红4号，CAS号 5858-39-9Note: The minimum requirements must correspond to the ionisation source used.注：最低标准应与使用的电离源相符合。TABLE IV 表4Level IV. In-use instrument checks 第四级 在用仪器检查Requirements for LC-MS液质联用仪要求Parameter to be checked需要检查的参数Typical tolerance limits典型允许限度As defined by the specific analysis method or according to the Ph. Eur. Or the MAH dossier由特定的分析方法定义或根据欧洲药典或MAH档案As defined in the used analysis method在使用的分析方法中定义The tests to be performed in Level IV are those in accordance with the system suitability of the analysis method in use.在第四级需要实施的检查是根据在用检验方法系统适用性来进行的。ANNEX I Level III. Periodic and motivated instrument checks 第三级 周期性主动仪器检查This Annex contains practical examples of tests and their associated tolerance limits for several parameters related to the performance of LC-MS. 本附件包括了LC-MS性能相关的几个参数的检查实例及其关联的允许限度。These examples can be considered by the OMCLs as possible approaches to perform the Level III of the equipment qualification process: “Periodic and motivated instrument checks”. 举例可以作为OMCL在实施第三级仪器确认过程“周期性主动仪器检查”中可能的方法。GENERAL CONSIDERATIONS 一般考虑- LC-MS is widely used for the identification of unknown substances or quantification of low concentrated substances where high specificity is needed. LC-MS广泛用于要求较高专属性时未知物质的鉴别，或低浓度物质的定量。MASS ACCURACY 质量准确度Materials: 材料Reserpine 利舍平Note: the selected concentration will depend on the instrument and experimental conditions. The laboratory should define the