การใช REFERENCE STANDARDS ในการควบค มค ณภาพยา

Transcription

1 การใช REFERENCE STANDARDS ในการควบค มค ณภาพยา น ดาพรรณ เร องฤทธ นนท ส าน กยาและว ตถ เสพต ด กรมว ทยาศาสตร การแพทย 23 ส งหาคม BDN 1

2 Definition Pharmaceutical Reference Standards A substance prepared for use as the standard in an assay, identification or purity test, whose relevant properties have been determined and are considered appropriate for its intended use(s). Pharmaceutical reference standards are required for comparative analytical methods which are included in a manufacturer s specification or pharmacopoeia monograph BDN 2

3 Test Methods in Pharmacopoeia; Required Reference Substances Infra red Spectrophotometry UV-Spectrophotometry Colorimetry Chromatographic method: TLC, GC, HPLC Non-stoichiometric Titration Microbiological assay Calibration of Instruments BDN 3

4 Classification of Reference Standards Primary Reference Standard Secondary Reference Standard (Working Standard) BDN 4

5 Classification of Reference Standards Primary Reference Standard A designated primary chemical reference substance is one that is widely acknowledged to have the appropriate qualities within a specified context, and whose value when use as an assay standard is accepted without requiring comparison to another chemical substance. ( WHO working document QAS/05.137) BDN 5

6 Classification of Reference Standards Secondary Reference Standard (Working Standard) A secondary chemical reference standard is a substance whose characteristics are assigned and/or calibrated by comparison with a primary chemical reference substance. ( WHO working document QAS/05.137) BDN 6

7 Primary Reference Standard USPRS : United States Pharmacopoeia Reference Standard BPCRS : British Pharmacopoeia Chemical Reference Standard EPCRS : European Pharmacopoeia Chemical Reference Standard ICRS : International Chemical Reference Standard NIBSC : National Institute of Biological Standard and Control BDN 7

8 Secondary Reference Standard ARS : ASEAN Reference Standard DMScRS : Department of Medical Sciences Reference Standard Inhouse working standards BDN 8

9 Use of Reference Standard Identification Test for impurities or degradation products Assay BDN 9

10 Use of Reference Standard Reference standards must be used consistently to ensure reliable measurements. Important to the user is the fact that the proper use of an reference standards BDN 10

11 Use of Reference Standard Intended information Period of validity Conditions for storage Instruction for use Intended use BDN 11

12 Use of Reference Standard Sources of information Certificate of Analysis Catalog book Recommendation document Label on the vial BDN 12

13 Use Reference Standard ICRS, ARS, DMScRS : Certificate of Analysis EPCRS, BPCRS : Catalog Book, Booklet USPRS : - Recommendation document - Label on the Vial NIBSC : Catalog Book BDN 13

14 Certificate of Analysis ICRS, ARS, DMScRS Assigned value with test methods employed Loss on drying / Water content Related substances / Degradation products Others : IR, Specific optical rotation Direction for use and storage BDN 14

15 Certificate of Analysis DEXAMETHASONE DMSc Reference Standard Control No Description : A white, crystalline powder. Infrared absorption : Concordant with the reference spectrum of Dexamethasone USPRS. Ultraviolet absorption : A % solution in methanol exhibits a maximum at 239 nm with A (1 %, 1 cm) about 399. Specific optical rotation : o ( 10 mg per ml, in dioxane) Chromatographic purity : Total impurities 0.34% (HPLC method) Loss on drying : 0.10 % BDN 15

16 Certificate of Analysis DEXAMETHASONE DMSc Reference Standard Control No Assay Intended use Direction for use Storage : % of C 22 H 29 FO 5, calculated on the dried basis, determined by HPLC method, compared with USPRS. : For chemical assay and identification. : Dry at 105 ๐ C for 3 hours before use. : Keep container tightly closed and protected from light, preferably at the temperature about 5 ๐ C. Tested Date : 8 July 2547 Next Retest Date : 8 July 2550 Reference Standard Center Bureau of Drug and Narcotic BDN 16

17 Catalog Book EPCRS List of substances, Purity Assigned content (as is) Where no drying conditions are stated, the substances is to be used as received Use : Code No 1 to BDN 17

18 The EPCRS are used in the following cases: Code Use 1. Identification by IR 2. Identification by TLC 3. Identification by Melting point 4. Identification by LC 6. Identification by GC 8. Identification by UV or Colorimetry 8A. Test for Related substances by UV or Colorimetry 9. Test for Related substances by TLC 10. Test for Related substances by LC BDN 18

19 The EPCRS are used in the following cases: Code Use 13. Test for related substances by GC 14. Assay by UV or Colorimetry 15. Assay by LC 16. Assay by GC 17. Microbiological Assay 20. Assay by Volumetric Titration 20A Assay by Hydrolysis Rate 21. General method 22. Other purpose; Enalapril for systen suitability BDN 19

20 Booklet BPCRS List of substances, content Declared content is quoted on an as is basis This figure is to be used in calculating the results of the assay Batch number on label corresponds with that given on booklet BDN 20

21 Recommendation document USPRS They are provided for use in the testes and assays of the official methods of USP / NF They are utilized at a value of 100.0%, unless so otherwise labeled BDN 21

22 Label on the Vial USPRS Example : Dry a portion at 105 ๐ C for 3 hours before using. Keep container tightly closed. Do not dry. Each mg of this material is equivalent to 857 mcg of minocycline on the as is basis BDN 22

23 Catalog Book NIBSC WHO International Reference Materials : Amikacin 1 st International Standard International Units per ampoule BDN 23

24 Storage In well-closed (tightly closed) containers protected from light Temperature Between 2 ๐ C and 10 ๐ C About 5 ๐ C Below 0 ๐ C / -10 ๐ C, -20 ๐ C BDN 24

25 Expiry Date WHO guideline : Chemical reference standards do not carry on expiry date Monitoring stability by regular re-examination of the collection by issuing body Any material that has deteriorated is replaced by new batches BDN 25

26 Expiry Date BPCRS : All BPCRS are supplied with at least 3 months shelf-life, the current Batch No is always listed on the website EPCRS : Official date in catalog Batch 1 valid until 30 June BDN 26

27 Expiry Date USPRS : Current Lot : O Previous Lot / valid use date : N (11/06) ARS : DMScRS WHO guideline Tested date, Next re-test date BDN 27

28 Website and E Address ICRS : who.apl@apoteket.se EPCRS : CRS@pheur.org BPCRS : queries@bpclab.co.uk BDN 28

29 Website and E Address USPRS : NIBSC : standards@nibsc.ac.uk enquiries@nibsc.ac.uk ARS, DMScRS : BDN 29

30 Thank you BDN 30

31 Definition Reference Material : ISO Guide 34 Material or substance one or more of whose properties are sufficiently homogeneous and well established to be used for the calibration of an apparatus, the assessment of a measurement method or for assigning values to materials BDN 31

32 Definition Certified reference material: ISO Guide 34 Reference material, accompanied by a certificate, one or more of whose property values are certified by a procedure which establishes its traceability to an accurate realization of the unit in which the property values are expressed, and for which each certified value is accompanied by an uncertainty at a stated level of confidence BDN 32