近日，EDQM-OMCL發(fā)布《紫外 - 可見(jiàn)分光光度計(jì)確認(rèn)指南》，包含Level III定期及有動(dòng)機(jī)的儀器檢查、紫外 - 可見(jiàn)分光光度計(jì)的建議及相關(guān)典型接受限、Level IV在用儀器檢查、一般注意事項(xiàng)、光譜狹縫寬度（如適用）、波長(zhǎng)精度、基線噪聲、光度漂移等內(nèi)容。文件將于9月1日生效。

 

 

 

ANNEX 3 OF THE OMCL NETWORK GUIDELINE “QUALIFICATION OF EQUIPMENT”

OMCL設(shè)備確認(rèn)指南附錄3

QUALIFICATION OF UV - VISIBLE SPECTROPHOTOMETERS
紫外-可見(jiàn)分光光度計(jì)的確認(rèn)

 

Note: Mandatory requirements in this annex are defined using the terms “shall” or “must”. The use of “should” indicates a recommendation. For these parts of the text other appropriately justified approaches are acceptable. The term “can” indicates a possibility or an example with non - binding character.
注：本附件中的強(qiáng)制性要求使用 “應(yīng)” 或 “必須” 等詞來(lái)定義。“宜” 的使用表示一種建議。對(duì)于文本的這些部分，其他有適當(dāng)理由的方法是可接受的。“可” 一詞表示一種可能性或一個(gè)不具約束力的示例。

 

Table of Contents
目錄

Introduction
簡(jiǎn)介

Level III. Periodic and motivated instrument checks
三級(jí)：定期及有動(dòng)機(jī)的儀器檢查

Recommendations for UV - visible spectrophotometers and related typical acceptance limits
紫外 - 可見(jiàn)分光光度計(jì)的建議及相關(guān)典型接受限

Level IV. In - use instrument checks
四級(jí)：使用中儀器檢查

Recommendations for UV - visible spectrophotometers and related typical acceptance limits
紫外 - 可見(jiàn)分光光度計(jì)的建議及相關(guān)典型接受限

Level III. Periodic and motivated instrument checks
三級(jí)：定期及有動(dòng)機(jī)的儀器檢查

General Considerations

一般注意事項(xiàng)

Spectral Slit Width (if applicable)

光譜狹縫寬度（如適用）

Wavelength Precision (for mechanically set wavelengths)

波長(zhǎng)精度（對(duì)于機(jī)械設(shè)定波長(zhǎng)）

Baseline Noise

基線噪聲

Photometric Drift

光度漂移

Level IV. In - use instrument checks
四級(jí)：使用中儀器檢查

 

Introduction

簡(jiǎn)介

 

The present document is the 3rd Annex of the core document “Qualification of Equipment”, and it shall be used in combination with it when planning, performing and documenting the UV - Visible spectrophotometer qualification process.
本文件是核心文件 “設(shè)備確認(rèn)” 的第 3 個(gè)附件，在規(guī)劃、執(zhí)行和記錄紫外 - 可見(jiàn)分光光度計(jì)確認(rèn)過(guò)程時(shí)，應(yīng)與該核心文件結(jié)合使用。

 

The core document contains the Introduction and general forms for Level I (Selection of instruments and suppliers) and II (Installation and release for use) of qualification, which are common to all types of instruments.
核心文件包含一級(jí)（儀器和供應(yīng)商的選擇）和二級(jí)（安裝和投入使用）確認(rèn)的簡(jiǎn)介和通用表格，這些適用于所有類型的儀器。

 

The present Annex 3 contains the Introduction and requirements for UV - Visible spectrophotometers. Level III (Periodic and motivated instrument calibration/checks) and IV (In - use instrument checks) qualifications must be carried out being ISO/IEC 17025 requirement.
本附件 3 包含紫外 - 可見(jiàn)分光光度計(jì)的簡(jiǎn)介和要求。三級(jí)（定期及有動(dòng)機(jī)的儀器校準(zhǔn) / 檢查）和四級(jí)（使用中儀器檢查）確認(rèn)必須按照 ISO/IEC 17025 要求進(jìn)行。

 

Requirements (if applicable) corresponding typical acceptance limits given in bold should be applied; however other appropriately justified approaches are acceptable.
應(yīng)采用（如適用）以粗體給出的相應(yīng)典型接受限；然而，其他有適當(dāng)理由的方法也是可接受的。

 

Exemplary procedures provided in this document have non - binding character. They can be helpful to carry out the required qualification. Nevertheless, it is left to the professional judgement and background experience of each OMCL to decide on the most relevant procedures to be undertaken in order to give evidence that their UV-Visible spectrophotometers are working properly and aresuitable for their intended use.

本文件中提供的示例程序不具約束力。它們可能有助于進(jìn)行所需的確認(rèn)。然而，由每個(gè) OMCL 根據(jù)專業(yè)判斷和背景經(jīng)驗(yàn)來(lái)決定采用最相關(guān)的程序，以證明其紫外 - 可見(jiàn)分光光度計(jì)工作正常且適合其預(yù)期用途。

 

If the qualification of equipment is done by the manufacturer or an external service - provider, it is the responsibility of the OMC L to make sure that this is in line with the requirements set out in this guideline.
如果設(shè)備的確認(rèn)是由制造商或外部服務(wù)提供商完成的，那么 OMCL 有責(zé)任確保其符合本指南中規(guī)定的要求。

 

Level III. Periodic and motivated instrument checks
三級(jí) 定期及有動(dòng)機(jī)的儀器檢查

 

recommendations for UV - visible spectrometers and related typical acceptance limits
對(duì)紫外 - 可見(jiàn)分光光度計(jì)的建議及相關(guān)典型接受限度

EDQM發(fā)布《紫外-可見(jiàn)分光光度計(jì)確認(rèn)指南》

following the instructions given in Ph. Eur. Chapter 2.2.25. "Control of equipment performance"
遵循《歐洲藥典》第 2.2.25 章 “設(shè)備性能控制” 中給出的說(shuō)明

 

Level IV. In - use instrument checks
四級(jí) 使用中儀器的檢查

 

Recommendations for UV - visible spectrophotometers and related typical acceptance limits
紫外 - 可見(jiàn)分光光度計(jì)的建議以及相關(guān)典型的可接受限度

EDQM發(fā)布《紫外-可見(jiàn)分光光度計(jì)確認(rèn)指南》

 

following the instructions given in Ph. Eur. Chapter 2.2.25. "Control of cuvettes"
按照歐洲藥典第 2.2.25 章 “比色皿的控制” 中給出的說(shuō)明操作

 

Level III. Periodic and motivated instrument checks
第三級(jí)：定期及有動(dòng)機(jī)的儀器檢查

 

This section contains practical examples of tests and their associated acceptance limits for several parameters related to the performance of a UV - visible spectrophotometer. These examples can be considered as the OPCs as possible approaches to perform the Level III of the equipment qualification process: "Periodic and motivated instrument checks".
本節(jié)包含了與紫外 - 可見(jiàn)分光光度計(jì)性能相關(guān)的幾個(gè)參數(shù)的測(cè)試實(shí)例及其相關(guān)的合格限。這些實(shí)例可被視為執(zhí)行設(shè)備確認(rèn)過(guò)程第三級(jí) “定期及有動(dòng)機(jī)的儀器檢查” 的可能方法（即操作規(guī)范條件）。

 

1.General Considerations

一般注意事項(xiàng)

 

Measurements made by comparing samples against external standards should be made under conditions during which temperature is held constant. This is particularly relevant where the carrier solvent is organic and measurements may be distorted by expansion or evaporation of the solvent.
通過(guò)將樣品與外部標(biāo)準(zhǔn)進(jìn)行比較而進(jìn)行的測(cè)量應(yīng)在溫度保持恒定的條件下進(jìn)行。這在載液為有機(jī)溶劑且測(cè)量可能因溶劑的膨脹或蒸發(fā)而失真的情況下尤為重要。

It is recommended to perform the qualification within the spectral range corresponding to the region of analytical interest.

建議在與分析感興趣區(qū)域相對(duì)應(yīng)的光譜范圍內(nèi)進(jìn)行確認(rèn)。

Ensure that the spectrophotometer has stabilised, according to the manufacturer's recommendations, before starting the qualification tests.

根據(jù)制造商的建議，在開(kāi)始確認(rèn)測(cè)試之前，確保分光光度計(jì)已穩(wěn)定。

When references are made to the European Pharmacopoeia, e.g. reagents R, then reagent quality shall comply with the Ph. Eur. specifications.

當(dāng)引用《歐洲藥典》時(shí)，例如試劑 R，那么試劑質(zhì)量應(yīng)符合《歐洲藥典》的規(guī)范。

When using commercial filters as alternative to the proposed tests, a set of filters covering the entire range of interest should be used. They should be calibrated with traceability to national/international standards, preferably through a national metrology laboratory or NIST.

當(dāng)使用商業(yè)濾光片替代建議的測(cè)試時(shí)，應(yīng)使用一組覆蓋整個(gè)感興趣范圍的濾光片。它們應(yīng)可溯源至國(guó)家 / 國(guó)際標(biāo)準(zhǔn)進(jìn)行校準(zhǔn)，最好通過(guò)國(guó)家計(jì)量實(shí)驗(yàn)室或美國(guó)國(guó)家標(biāo)準(zhǔn)與技術(shù)研究院（NIST）進(jìn)行。

 

2.Spectral Slit Width (if applicable)

光譜狹縫寬度（如適用）

 

When using an instrument on which the slit - width is variable at the selected wavelength, the slit width must be small compared with the half - width of the absorption band but it must be as large as possible to obtain a high value of Ia. Therefore, a slit - width is chosen such that further reduction does not result in a change in absorbance reading.
當(dāng)使用在選定波長(zhǎng)下狹縫寬度可變的儀器時(shí)，狹縫寬度必須與吸收帶的半寬度相比很小，但又必須盡可能大以獲得高的 Ia 值。因此，選擇的狹縫寬度應(yīng)使得進(jìn)一步減小不會(huì)導(dǎo)致吸光度讀數(shù)的變化。

 

Method and Limits
方法和限度

 

1.Switch the system on and start the Scan module.

開(kāi)啟系統(tǒng)并啟動(dòng)掃描模塊。

2.Select SETUP and set the following parameters:

選擇 “設(shè)置” 并設(shè)置以下參數(shù)：

 

X Mode = Nanometers

X 模式 = 納米

Start wavelength = 650.0 nm

起始波長(zhǎng) = 650.0 納米

Stop wavelength = 660.0 nm

終止波長(zhǎng) = 660.0 納米

Scan mode = Single

掃描模式 = 單次

Scan rate = 100 nm/min

掃描速率 = 100 納米 / 分鐘

Gain = (100) see 4 below

增益 = （100）見(jiàn)下面第 4 點(diǎn)

 

3.Select Options tab and set the following parameters:

選擇 “選項(xiàng)” 選項(xiàng)卡并設(shè)置以下參數(shù)：

 

SWB = 4 nm

狹縫寬度帶寬 = 4 納米

Scan mode = Single front

掃描模式 = 單次前向

Lamps on = Deuterium

燈開(kāi)啟 = 氘燈

Source change = 700.0 nm

光源切換 = 700.0 納米

 

4.Start a scan and examine the trace for a spectral peak around 656.1 nm. If no peak is seen or it is less than 50 % T, increase the gain.

開(kāi)始掃描并檢查在 656.1 納米附近的光譜峰的軌跡。如果看不到峰或其小于 50% 透光度（T），則增加增益。

 

5.Measure the width of the peak (in nanometres) at half the height of the peak.
測(cè)量峰高一半處的峰寬（單位：納米）。

 

This represents the spectral bandwidth and should be within ± 10% of that selected via the computer.
這代表光譜帶寬，其值應(yīng)在通過(guò)計(jì)算機(jī)選擇的值的 ±10% 范圍內(nèi)。

 

6.Check the calibration at a slit width of 0.2 nm.
在狹縫寬度為 0.2 納米時(shí)檢查校準(zhǔn)情況。

 

If the measured slits are too small then, for a selected width, the instrument will have more photometric noise than normal.
如果測(cè)量的狹縫過(guò)小，那么對(duì)于選定的寬度，儀器將產(chǎn)生比正常情況更多的光度噪聲。

 

If the slit width is unacceptable, then reset the slit calibration.
如果狹縫寬度不可接受，則重置狹縫校準(zhǔn)。

EDQM發(fā)布《紫外-可見(jiàn)分光光度計(jì)確認(rèn)指南》

Effect of spectral slit width on absorbance fluctuation (performed with pure solvents).
光譜狹縫寬度對(duì)吸光度波動(dòng)的影響（使用純?nèi)軇┻M(jìn)行）。

EDQM發(fā)布《紫外-可見(jiàn)分光光度計(jì)確認(rèn)指南》

 

3.Wavelength Precision (for mechanically set wavelengths)

3. 波長(zhǎng)精度（針對(duì)機(jī)械設(shè)定波長(zhǎng)）

 

Materials:
材料：

 

For this test, the same materials of the previous test can be used: Holmium perchlorate solution R prepared, for example, with a 40 g/L solution of holmium oxide R in a solution of perchloric acid R containing 141 g/L of HClO4 (Ph. Eur. Chapter 4.1.1. "Reagents", ref. 1043101).
對(duì)于此測(cè)試，可以使用與之前測(cè)試相同的材料：例如，將氧化鈥 R 的 40 g/L 溶液在含有 141 g/L 高氯酸（HClO4）的高氯酸 R 溶液中制備的高氯酸鈥溶液 R（歐洲藥典第 4.1.1 章 “試劑”，參考文獻(xiàn) 1043101）。

 

If available, the built - in mercury lamp of the instrument may be used for this test. Alternatively, suitable commercial certified filters may be used1.
如果有儀器內(nèi)置的汞燈，可用于此測(cè)試?；蛘撸部墒褂煤线m的商業(yè)認(rèn)證濾光片 1。

 

Method:
方法：

 

Carry out 6 measurements of the absorbance maxima.
對(duì)吸光度最大值進(jìn)行 6 次測(cè)量。

 

Limits:
限度：

 

Repeatability: the relative standard deviation of the absorbance maxima should satisfy the manufacturer's specifications.
重復(fù)性：吸光度最大值的相對(duì)標(biāo)準(zhǔn)偏差應(yīng)符合制造商的規(guī)格要求。

 

The difference between the 6 individual absorbance maxima values should comply with the manufacturer's specifications (e.g. < 0.5 nm).
6 個(gè)單獨(dú)的吸光度最大值之間的差值應(yīng)符合制造商的規(guī)格要求（例如 < 0.5 nm）。

 

4.Baseline Noise

基線噪聲

 

For this test, 2 alternative methods are proposed.
對(duì)于此測(cè)試，提出了兩種替代方法。

 

TEST 1
測(cè)試 1

 

Method:
方法：

Make 61 absorbance measurements with an integration time of 1 second at a wavelength of 500 nm, with no sample in the sample chamber, and calculate the mean.
在 500 納米波長(zhǎng)下，積分時(shí)間為 1 秒，在樣品室中無(wú)樣品的情況下進(jìn)行 61 次吸光度測(cè)量，并計(jì)算平均值。

 

Limits:
限度：

Mean ± 0.002 Absorbance units
平均值 ± 0.002 吸光度單位

 

TEST 2
測(cè)試 2

 

Method:
方法：

Record the absorbance for 60 seconds at 200, 300 and 400 nm with a highly pure, synthetic Quartz block¹. The measurement is made against air.
使用高純度合成石英塊在 200、300 和 400 納米處記錄 60 秒的吸光度。測(cè)量以空氣為參比。

 

Note: If commercial filters are used, the wavelengths and the exact absorption values with the corresponding tolerance limits will depend on the type of filters.
注意：如果使用商用濾光片，波長(zhǎng)以及確切的吸收值和相應(yīng)的容差限度將取決于濾光片的類型。

 

Example of limits:
限度示例：

EDQM發(fā)布《紫外-可見(jiàn)分光光度計(jì)確認(rèn)指南》

 

Photometric Drift
光度漂移

 

Photometric drift should be checked at both the visible and UV region, at appropriate wavelengths. The limits are in accordance with the user's requirements (as defined in Level I) and with manufacturer's specifications.
光度漂移應(yīng)在可見(jiàn)光和紫外光區(qū)域的適當(dāng)波長(zhǎng)下進(jìn)行檢查。其限度應(yīng)符合用戶要求（如一級(jí)所定義）和制造商的規(guī)格。

 

For this test, 2 alternative examples are proposed.
對(duì)于此測(cè)試，提出了兩個(gè)替代示例。

 

TEST 1
測(cè)試 1

 

Method:
方法：

 

As routine test, the drift is measured at 250 nm over a period of 2 hours by using the Time Scan mode of the instrument, with no sample in the sample chamber.
作為常規(guī)測(cè)試，在樣品室無(wú)樣品的情況下，使用儀器的時(shí)間掃描模式在 250 納米波長(zhǎng)下測(cè)量 2 小時(shí)內(nèi)的漂移。

 

Limits: ± 0.001 Absorbance units/h
限度：±0.001 吸光度單位 / 小時(shí)

 

Note: In certain cases, for example when several samples are measured over a long period of time (or when using auto sampler), the drift can also be determined at the wavelength reported in the analytical method, under the same operational conditions, before testing samples.
注意：在某些情況下，例如在長(zhǎng)時(shí)間測(cè)量多個(gè)樣品時(shí)（或使用自動(dòng)進(jìn)樣器時(shí)），也可以在測(cè)試樣品之前，在相同操作條件下，在分析方法中報(bào)告的波長(zhǎng)處測(cè)定漂移。

 

TEST 2
測(cè)試 2

 

Method.
方法

 

Record the baseline for 60 minutes at 500 nm and compare the absorbance with the initial value.
在 500 納米處記錄 60 分鐘基線，并將吸光度與初始值進(jìn)行比較。

 

Limits: ± 0.002 Absorbance units/h
限度：±0.002 吸光度單位 / 小時(shí)

 

Level IV. In - use instrument checks
IV 級(jí) 使用中儀器檢查

 

This Annex contains practical examples of tests and their associated acceptance limits for several parameters related to the performance of an UV - Visible spectrophotometer. 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”.
本附錄包含了與紫外 - 可見(jiàn)分光光度計(jì)性能相關(guān)的幾個(gè)參數(shù)的測(cè)試實(shí)例及其相關(guān)的可接受限度。這些實(shí)例可被官方藥品控制實(shí)驗(yàn)室（OMCLs）視為執(zhí)行設(shè)備確認(rèn)過(guò)程 IV 級(jí) “使用中儀器檢查” 的可行方法。

 

SYSTEM SUITABILITY TEST OF THE METHOD
方法的系統(tǒng)適用性測(cè)試

 

REPEATABILITY (for quantitative analysis)

重復(fù)性（用于定量分析）

RESOLUTION (for both qualitative and quantitative analysis)

分辨率（用于定性和定量分析）

 

Method:
方法：

 

This test should be performed according to Ph. Eur., the MAH dossier or a suitably validated in - house method.
此測(cè)試應(yīng)根據(jù)《歐洲藥典》、上市許可持有人（MAH）檔案或經(jīng)過(guò)適當(dāng)驗(yàn)證的內(nèi)部方法進(jìn)行。

 

 

 

 

 

本文由廣州佳譽(yù)醫(yī)療器械有限公司/佛山浩揚(yáng)醫(yī)療器械有限公司聯(lián)合編輯