European Pharmacopoeia 5.0
In FTIR Validation, we discussed validation methods for infrared spectrophotometers. We introduced the European Pharmacopoeia 4.0 as one of the standards for the infrared of spectrophotometers. Content related to infrared spectrophotometers is described in the section "2.2.24 Absorption Spectrophotometry, Infrared", and instrument validation methods are described under the items "Control of resolution performance" and "Verification of the wave-number scale".
In 2005, the European Pharmacopoeia 5.0 was introduced, and these standards were revised. In this article, we introduce the points of revision and how the Shimadzu FTIR series addresses these changes.
Revised Points
The items that were revised in revision relate to Fourier Transform infrared spectrometers (FTIR). There were no changes relating to dispersive infrared spectrophotometers.
Changes in Control of Resolution Performance
The description given in the European Pharmacopoeia 5.0 is as follows.
| For Fourier-transform instruments, … for example by recording the spectrum of a polystyrene film approximately 35 μm in thickness. The differences between the absorbances at the absorption minimum at 2870 cm-1 and the absorption maximum at 2849.5 cm-1 is greater than 0.33. The differences between the absorbances at the absorption minimum at 1589 cm-1 and the absorption maximum at 1583 cm-1 is greater than 0.08. |
There was a change from the use of transmittance measurement of spectra in the European Pharmacopoeia 4.0 to the use of spectra obtained by absorbance measurement, and the resolution standard is now specified according to absorbance measurement exclusively.
Changes in Verification of Wave-number Scale
The verification of wavenumber scale in the European Pharmacopoeia 5.0 is as specified below.
| 3060.0 (±1.0) cm-1 2849.5 (±1.0) cm-1 1942.9 (±1.0) cm-1 1601.2 (±1.0) cm-1 1583.0 (±1.0) cm-1 1154.5 (±1.0) cm-1 1028.3 (±1.0) cm-1 |
The wavenumber verification criteria in European Pharmacopoeia 4.0 specified as ±1.5 for the three wavenumbers 3060.0, 2849.5 and 1942.9 cm-1 was changed to an allowable variance of ±1.0 in the new standard.
Validation Program Supporting European Pharmacopoeia 5.0
The validation program supporting the European Pharmacopoeia 5.0 is included in IRsolution Ver. 1.30.
In both the Japanese Pharmacopoeia and European Pharmacopoeia 4.0, instrument performance evaluation is based on the 5 test items: (1) power spectrum, (2) resolution, (3) wavenumber accuracy, (4) wavenumber repeatability and (5) absorbance reproducibility.
1. Power Spectrum
Although not included in the European Pharmacopoeia 5.0, this test is used to evaluate the most basic performance of the FTIR. The test procedure is the same in the validation program for both the Japanese Pharmacopoeia and European Pharmacopoeia 4.0. This test compares the intensity of the power spectrum at a specified wavenumber to the criterion values. When the measured intensity is equal or larger than the criterion value, the test is passed.
2. Resolution
This is as described above. A pass rating is assessed if each of the absorbance values is equal to or greater than the respective criterion value.
3. Wavenumber Accuracy
This is as described above. A pass rating is assessed if each of the wavenumber measurement values is within the specified variance.
4. Wavenumber Reproducibility
Although this test is not included in the European Pharmacopoeia 5.0, this is regarded as a test item due to standardization with the Japanese Pharmacopoeia. The test procedure is the same in the validation program for both the Japanese Pharmacopoeia and European Pharmacopoeia 4.0.
Polystyrene film is measured twice, and the peak wavenumbers are compared at three specified points. The program assesses whether or not the difference between the two measurement results is within the permissible range. If the difference in peak wavenumbers is within the permissible range at all three specified points, a pass rating is assessed.
5. Absorbance Reproducibility
Although this test is not included in the European Pharmacopoeia 5.0, this is regarded as a test item due to standardization with the Japanese Pharmacopoeia. The test procedure is the same in the validation program for both the Japanese Pharmacopoeia and European Pharmacopoeia 4.0. The permissible range according to the Japanese Pharmacopoeia is 0.5 %, expressed in transmittance; however, in the validation program that supports the European Pharmacopoeia 5.0, transmittance values that fluctuate ±0.5 % from the transmittance at the test wavenumber are converted to absorbance, and are then evaluated with respect to the permissible range. For example, the absorbance of the 2849.5 cm-1 peak is about 1 ABS (about 10 % transmittance), so the absorbance fluctuation (±0.03 ABS) corresponding to the ±0.5 % transmittance fluctuation is considered the permissible range. Polystyrene film is measured twice, and the absorbance values are compared at three specified points. The program assesses whether or not the difference between the two measurement results is within the permissible range. If the difference in absorbances is within the permissible range at all three specified points, a pass rating is assessed.
Support for European Pharmacopoeia 5.0 in Shimadzu FTIR Series
The European Pharmacopoeia 5.0 is supported by IRsolution Ver. 1.30 and the included validation program. The supported instruments are the IRPrestige-21 and FTIR8400S, 8300, 8400 (as of noviembre 1, 2006). To enable support for the European Pharmacopoeia 5.0 in IRPrestige-21 and FTIR-8400S instruments already in operation, please contact your Shimadzu representative to upgrade IRsolution to Ver. 1.30.
Standardizing Validation Standards of Japanese Pharmacopoeia and European Pharmacopoeia 5.0
The European Pharmacopoeia is, as the name indicates, the compilation of standards that apply to the European Union (EU).When products are shipped into the EU, they often require instrument validation complying with the European Pharmacopoeia 5.0. On the other hand, in Japan, compliance with the Japanese Pharmacopoeia is fundamental. The Japanese Pharmacopoeia is periodically revised, often with a view to linking it with the pharmacopoeia of other countries. The Japanese Pharmacopoeia infrared absorption spectrum measurement method was linked to the European Pharmacopoeia 4.0 in Revision 14, Supplement 1.With the release of the European Pharmacopoeia 5.0, differences with the Japanese Pharmacopoeia again occurred; however, it is likely that re-linking of the standard will occur in the near future with another revision. (However, as of 1 de noviembre de 2006, there is no information regarding revision of the Japanese Pharmacopoeia infrared absorption spectrum measurement method.)
