Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
DEFINITION
Nabumetone Oral Suspension contains Nabumetone in a suitable flavoured vehicle.
The oral suspension complies with the requirements stated under Oral Liquids and with the following requirements.
Content of nabumetone, C15H16O2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Add a volume of the well-shaken suspension containing 0.1 g of Nabumetone to 10 mL of dichloromethane, shake, allow to separate and use the lower layer.
(2) 1.0% w/v of nabumetone BPCRS in dichloromethane.
(3) A mixture of equal volumes of solutions (1) and (2).
CHROMATOGRAPHIC CONDITIONS
(a) Use a silica gel GF254 precoated plate (Merck 5715 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 2 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air and examine under ultraviolet light (254 nm).
MOBILE PHASE
dichloromethane
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) is similar in position and colour to the spot in the chromatogram obtained with solution (2) and the chromatogram obtained with solution (3) shows a single, compact spot at the same Rf value as the spot in the chromatogram obtained with solution (2).
B. In the Assay the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the peak in the chromatogram obtained with solution (2).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a volume of the suspension containing 0.5 g of Nabumetone with 10 mL of methanol until completely dispersed, add sufficient acetonitrile to produce 100 mL, shake for a further 5 minutes and filter (Whatman No. 1 paper is suitable).
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) 0.0015% w/v of nabumetone impurity F EPCRS in acetonitrile.
(4) 0.002% w/v of each of nabumetone BPCRS and nabumetone impurity D BPCRS in acetonitrile.
(5) Dilute 1 volume of solution (2) to 10 volumes with acetonitrile.
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
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) To a weighed quantity of the suspension containing 0.1 g of Nabumetone, add 70 mL of ethanol (96%), mix with the aid of ultrasound for 45 minutes, add sufficient ethanol (96%) to produce 100 mL and filter (Whatman GF/C paper 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
Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C15H16O2, weight in volume, from the chromatograms obtained using the declared content of C15H16O2 in nabumetone BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Nabumetone.
