欧洲药典质量标准的起草技术指南,英文版

European Directorate for the Quality of Medicines & HealthCare

6

© Council of Europe, 67075 Strasbourg Cedex, France - 2011

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Making copies of this fi le for commercial purposes or posting this fi le on a web site that is open to public consultation is strictly prohibited.

TECHNICAL GUIDE FOR THE ELABORATION OF MONOGRAPHS

6th Edition – 2011

CONTENTS

1.INTRODUCTION (6)

1.1.P URPOSE OF THE G UIDE (6)

1.2.T EST PROCEDURES (6)

1.3.E QUIPMENT (7)

1.4.Q UANTITIES (7)

1.5.R EAGENTS (9)

1.6.C OMMERCIAL NAMES (9)

1.7.R EFERENCE STANDARDS (10)

2.MONOGRAPH ON A SUBSTANCE FOR PHARMACEUTICAL USE (10)

2.1.D EFINITION (11)

binations (12)

2.1.2.Content (12)

2.2.C HARACTERS (14)

2.2.1.Appearance (14)

2.2.2.Taste (15)

2.2.3.Odour (15)

2.2.4.Solubility (15)

2.2.5.Stability factors (15)

2.2.6.Hygroscopicity (15)

2.2.7.Solid-state properties (16)

2.2.8.Other characteristics (16)

2.2.9.Behaviour in solution (16)

2.3.I DENTIFICATION (17)

2.3.1.General (17)

2.3.1.1.Methods requiring complex instrumentation (18)

2.3.1.2.Other methods (18)

2.3.2.Infrared absorption spectrophotometry (18)

2.3.2.1.Salts of organic acids or bases (18)

2.3.2.2.Chemically related substances (18)

2.3.2.3.Polymorphism (19)

2.3.2.4.Optical isomers (19)

2.3.3.Ultraviolet and visible absorption spectrophotometry (19)

2.3.4.Melting point, freezing point and boiling point (20)

2.3.5.Specific optical rotation (21)

2.3.6.Thin-layer chromatography (21)

2.3.7.Gas chromatography and liquid chromatography (21)

2.3.8.Chemical reactions (22)

2.4.T ESTS (22)

2.4.1.General (22)

2.4.2.Titles (22)

2.4.3.Solution S (23)

2.4.4.Appearance of solution (24)

2.4.4.1.Clarity and degree of opalescence (24)

2.4.4.2.Degree of coloration (25)

2.4.5.pH and Acidity or alkalinity (25)

2.4.6.Optical rotation (27)

2.4.7.Absorption spectrophotometry (ultraviolet and visible) (27)

2.4.8.Related substances (28)

2.4.8.1.Thin-layer chromatography (TLC) (32)

2.4.8.2.Liquid chromatography (LC) (33)

2.4.8.3.Gas-liquid chromatography (GC) (37)

2.4.8.4.Capillary electrophoresis (CE) (38)

2.4.9.Readily carbonisable substances (39)

2.4.10.Foreign anions and/or cations (39)

2.4.11.Heavy metals (40)

2.4.12.Loss on drying (41)

2.4.13.Thermogravimetry (2.2.34) (42)

2.4.14.Semi-micro determination of water (Karl Fischer – 2.5.12) (42)

2.4.15.Micro determination of water (2.5.32) (42)

2.4.16.Gas chromatographic determination of water (43)

2.4.17.Determination of water by distillation (2.2.13) (43)

2.4.18.Sulfated ash (2.4.14) (43)

2.4.19.Residue on evaporation (43)

2.4.20.Residual solvents (43)

2.5.A SSAY (44)

2.5.1.Ultraviolet and visible spectrophotometry (44)

2.5.1.1.Direct measurement (44)

2.5.1.2.Measurement after a colour reaction (45)

2.5.2.Volumetric analysis (45)

2.5.3.Chromatography (46)

2.5.4.Determination of nitrogen by sulfuric acid digestion (semi-micro method) (46)

2.6.S TORAGE (46)

2.7.L ABELLING (47)

2.8.I MPURITIES (47)

2.9.F UNCTIONALITY-RELATED CHARACTERISTICS (47)

3.ANALYTICAL VALIDATION (48)

3.1.D EFINITIONS AND TERMINOLOGY (48)

3.1.1.Introduction (48)

3.1.2.Types of analytical procedures to be validated (48)

3.1.3.Validation characteristics and requirements (49)

3.1.4.Glossary (50)

3.2.M ETHODOLOGY (52)

3.2.1.Introduction (52)

3.2.2.Specificity (53)

3.2.2.1.Identification (53)

3.2.2.2.Assays and impurity tests (53)

3.2.3.Linearity (54)

3.2.4.Range (54)

3.2.5.Accuracy (55)

3.2.5.1.Assay (55)