The latest revision of European Pharmacopoeia to 5.2, and its effect on the Qualification of UV-Visible. Visible spectrophotometers

Transcription

1 The latest revision of European Pharmacopoeia to 5.2, and its effect on the Qualification of UV-Visible Visible spectrophotometers JOHN P. HAMMOND CSci CChem FRSC Optiglass Ltd., 52/54 Fowler Rd, Hainault, IG6 3UT, UK

2 Structure Introduction. Background Pharmacopoeia requirements. Control Parameters. Changes in 5.2 Use of Accreditation. Conclusions and future developments.

3 Introduction UV-Vis Vis essentially accurate and precise. Essential requirement to qualify system for use in the pharmaceutical industry, and prove evidence on control.

4 Instrument Qualification

5 Instrument Qualification

6 Instrument Qualification

7 Introduction Pharmacopoeia have always detailed the control parameters. Latest updates reflect acceptance of independently certified reference materials.

8 Background Pharmacopoeia requirements Fully documented in section Absorption Spectrophotometry, Ultraviolet and Visible. Key sections: Control of wavelengths. Control of absorbance. Limit of stray light. Resolution.

9 Control Parameters - UV-Visible Visible Wavelength control * Mercury emission * Deuterium emission * Holmium Oxide / Perchloric acid solution

10 UV-Visible Visible Wavelength Calibration Sample beam intensity (I units) Wavelength (nm) Mercury arc source * Recommended by Pharmacopoeias and ASTM E275 * Multiple lines through UV and Visible * Traceable as a fundamental physical constant

11 UV-Visible Visible Wavelength Calibration Deuterium Lamp Emission Line * Lamp may already be installed in the instrument? * Only two emission lines, both in the visible ( and nm) * Traceable as a fundamental constant of nature

12 UV-Visible Visible Wavelength Calibration Holmium liquid Absorbance Wavelength (nm) Holmium Oxide / Perchloric Acid Solution * Multiple peaks in the UV and Visible * Solution is sufficiently well defined to allow for peak value assignment with an acceptable uncertainty budget * Bandwidth dependent

13 Control Parameters - UV-Visible Visible Wavelength control Mercury emission Deuterium emission Holmium Oxide / Perchloric acid solution Absorbance control Absorbance control * Potassium Dichromate (K 2 Cr 2 O 7 ) solution

14 UV-Visible Visible Absorbance Accuracy Absorbance Potassium Dichromate Solutions Wavelength (nm) 20 mg/l 40 mg/l 60 mg/l 80 mg/l 100 mg/l K 2 Cr 2 O 7 Solution * Recommended by Pharmacopoeias * Four peaks/troughs in the UV * Involved preparation * Contamination and solution accuracy an issue. * Which acidic media? * Available in sealed cells with nominal concentration values of 20, 40, 60, 80 and 100 mg/l.

15 Control Parameters - UV-Visible Visible Wavelength control Mercury emission Deuterium emission Holmium Oxide / Perchloric acid solution Absorbance control Potassium Dichromate (K 2 Cr 2 O 7 ) solution Stray Light Stray Light * Potassium Chloride (KCl) solution

16 Stray Light Tests for non-specific Absorbance Monochromator efficiency Becomes a larger problem at short wavelengths Higher scattering - especially in PDA instruments Lower available lamp energy Pharmacopoeias recommend Potassium Chloride (KCl) solution Absorbance at 198 nm above 2.0 A for 12g/l solution

17 Potassium Chloride (1.2 % m/v) Potassium chloride stray light solution 5 Absorbance Wavelength (nm)

18 Control Parameters - UV-Visible Visible Wavelength control Mercury emission Deuterium emission Holmium Oxide / Perchloric acid solution Absorbance control Potassium Dichromate (K 2 Cr 2 O 7 ) solution Stray Light Potassium Chloride (KCl) solution Resolution * Toluene / Hexane

19 UV-Visible Visible Resolution (Bandwidth) Absorbance Toluene in Hexane SBW 0.5 nm SBW 1.0 nm SBW 1.5 nm SBW 1.7 nm SBW 1.8 nm SBW 2.0 nm SBW 3.0 nm 0.020% v/v Toluene/Hexane Solution * Recommended in Pharmacopoeias * Volatile solvents * Bandwidth 1.7nm or less to pass E.P. criteria (1.5 ratio) * Measures resolution in UV only Wavelength (nm)

20 Changes in 5.2

21 Changes in 5.2 Highlighted in text Use of a 600 mg/l Potassium Dichromate solution to establish Control of Absorbance at 430 nm. Use of Potassium Chloride for Limit of stray light. Use of suitable certified reference materials. Issued in Jan for implementation on July

22 Use of a 600 mg/l Potassium Dichromate solution at 430 nm. Initial work published in Pharmeuropa Vol. 15, No. 4, October A collaborative trial of 13 pharmaceutical laboratories, both in commercial and regulatory organizations across Europe. Work evaluated a 600 mg/l solution of potassium dichromate in M sulfuric acid. Established the mean specific absorbance at /- 0.2 ( / A) No stability data?

23 Use of a 600 mg/l Potassium Dichromate solution at 430 nm. Stability study initiated in March Consists of 5x references of each of the following: Neutral Density glass at 0.95 A. 600 mg/l potassium dichromate solution in M sulfuric acid. 600 mg/l potassium dichromate solution in M perchloric acid. Results to date:

24 Use of a 600 mg/l Potassium Dichromate solution at 430 nm. 600 mg/l Potassium dichromate 430 nm A Absorbance (Δ A) Mar Jun Sep-05 1-Jan Apr Perchloric Sulfuric N.G. Glass Linear (Perchloric) Linear (Sulfuric) Linear (N.G. Glass) Date

25 Use of Potassium Chloride for Limit of stray light. Potassium chloride stray light solution 5 Absorbance Wavelength (nm)

26 Use of Potassium Chloride for Limit of stray light. EUROPEAN PHARMACOPOEIA SUPPLEMENT 2000 Limit of stray light. Stray light may be detected at a given wavelength with suitable filters or solutions: for example the absorbance of a 12 g/l solution of potassium chloride R in a 1 cm cell must be greater than 2 at 200 nm when compared with water R as the compensation liquid. Potassium chloride stray light solution 5 Absorbance Wavelength (nm)

27 Use of Potassium Chloride for Limit of stray light. EUROPEAN PHARMACOPOEIA 4 Limit of stray light. Stray light may be detected at a given wavelength with suitable filters or solutions: for example the absorbance of a 12 g/l solution of potassium chloride R in a 1 cm cell increases steeply between 220 and 200nm, and is greater than 2 at a wavelength between 198 and 202 nm when compared with water R as the compensation liquid. Potassium chloride stray light solution 5 Absorbance Wavelength (nm)

28 Use of Potassium Chloride for Limit of stray light. EUROPEAN PHARMACOPOEIA 5.2 Limit of stray light. Stray light may be detected at a given wavelength with suitable filters or solutions: for example the absorbance of a 12 g/l solution of potassium chloride R in a 1 cm cell increases steeply between 220 and 200nm, and is greater than 2.0 at 198 nm when compared with water R as the compensation liquid. Suitable certified reference materials may also be used. Potassium chloride stray light solution 5 Absorbance Wavelength (nm)

29 Use of suitable certified reference materials. Define suitable? Materials produced in a ISO / Guide 34 accredited calibration laboratory. Why an accredited laboratory?

30 Accreditation to ISO 17025/Guide 34 Before accreditation. A calibration laboratory producing an acceptable product will have most of the aspects required for accreditation, but it s unlikely that all will be present? Some low level procedures are likely to be being performed without documentation? Traceability chain may be incomplete or broken? Structured assessment of uncertainty budget may not have been performed, and therefore reported on the certification?

31 Accreditation to ISO 17025/Guide 34 ISO 17025/Guide 34 accreditation: Requires an objective initial evaluation. Requires full (and appropriate) documentation of all procedures for both manufacture and certification. Requires a proven and working traceability chain. Requires documented, structured assessment of the Uncertainty budget, in accordance with ISO published guidelines. * Installs a discipline and a philosophy where continuous improvement is a primary goal. * G.U.M. Guide to the Uncertainty of Measurement, ISO, 1995.

32 Conclusions v5.2 provides a up-to to-date procedures for providing evidence of control. Suitable certified reference materials (CRMs( CRMs) ) do have the capability to isolate the instrumentation from the laboratory thereby providing an easier solution to OOS situations. ISO 17025/Guide 34 accreditation provides the third party endorsement of the process and product certification which produces the CRMs.

33 Don t risk it

34 Future developments Further revision of Euro. Pharm.? Harmonization of E.P./J.P./U.S.P. protocols via ICH protocols.