Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
DEFINITION
Nabumetone Tablets contain Nabumetone.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of nabumetone, C15H16O2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
The infrared absorption spectrum of the powdered tablets, Appendix II A, is concordant with the reference spectrum of nabumetone (RS 239).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in acetonitrile.
(1) Shake a quantity of the powdered tablets containing 0.25 g of Nabumetone with 50 mL of acetonitrile, filter through a glass-fibre filter (Whatman GF/C is suitable) and use the filtrate.
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) 0.0015% w/v of nabumetone impurity F EPCRS.
(4) 0.002% w/v of each of nabumetone BPCRS and nabumetone impurity D BPCRS.
(5) Dilute 1 volume of solution (2) to 10 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with base-deactivated octadecylsilyl silica gel for chromatography (4 µm) (Genesis C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
Mobile phase A 12 volumes of tetrahydrofuran, 28 volumes of acetonitrile and 60 volumes of a 0.1% v/v solution of glacial acetic acid in carbon dioxide-free water.
Mobile phase B 24 volumes of tetrahydrofuran, 56 volumes of acetonitrile and 20 volumes of a 0.1% v/v solution of glacial acetic acid in carbon dioxide-free water.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-12 | 100 | 0 | isocratic |
| 12-28 | 100→0 | 0→100 | linear gradient |
| 28-33 | 0 | 100 | isocratic |
| 33-34 | 0→100 | 100→0 | linear gradient |
| 34-35 | 100 | 0 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to nabumetone (retention time about 11 minutes) are: impurity D, about 1.1 and impurity F, about 2.7.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the two principal peaks is at least 1.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity F is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.3%);
the area of any other secondary peak is not greater than 0.4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any other secondary peaks is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (5) (0.05%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) To a quantity of powdered tablets containing 0.5 g of Nabumetone, add 400 mL of acetonitrile, mix with the aid of ultrasound, allow to cool, add sufficient acetonitrile to produce 500 mL, mix and filter through a glass-fibre filter (Whatman GF/C is suitable). Dilute 1 volume of the filtrate to 20 volumes with the mobile phase.
(2) Dilute 1 volume of a 0.1% w/v solution of nabumetone BPCRS in acetonitrile to 20 volumes with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with base-deactivated octadecylsilyl silica gel for chromatography (4 µm) (Genesis C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
18 volumes of tetrahydrofuran, 40 volumes of a 0.1% v/v solution of glacial acetic acid in carbon dioxide-free water and 42 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions the retention time of nabumetone is about 4 minutes.
DETERMINATION OF CONTENT
Calculate the content of nabumetone, C15H16O2, in the tablets from the chromatograms obtained and using the declared content of C15H16O2 in nabumetone BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Nabumetone.
