Nabumetone Oral Suspension

General Notices

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 chloroform, shake, allow to separate and use the lower layer.
(2) 1.0% w/v of nabumetone BPCRS in chloroform.
(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

chloroform

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).

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) 0.0025% w/v of nabumetone BPCRS in acetonitrile.
(3) 0.0015% w/v of nabumetone impurity F BPCRS in acetonitrile.
(4) 0.002% w/v of each of nabumetone BPCRS and nabumetone impurity D BPCRS in 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 4µ is suitable).
(b) Use gradient elution and the mobile phases 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.

When the chromatograms are recorded under the prescribed conditions the retention time of nabumetone is about 11 minutes.

mobile phase
Mobile phase A12 volumes of tetrahydrofuran, 28 volumes of acetonitrile for chromatography and 60 volumes of a 0.1% v/v solution of glacial acetic acid in carbon dioxide-free water.
Mobile phase B24 volumes of tetrahydrofuran, 56 volumes of acetonitrile for chromatography and 20 volumes of a 0.1% v/v solution of glacial acetic acid in carbon dioxide-free water.
system suitability

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution factor 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 nabumetone impurity F is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.3%);

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 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add to a weighed quantity of the suspension containing 1 g of Nabumetone 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 5 volumes of the filtrate to 100 volumes with the mobile phase and further dilute 5 volumes of the resulting solution to 50 volumes with the mobile phase.
(2) Dilute 5 volumes of a 0.1% w/v solution of nabumetone BPCRS in acetonitrile to 100 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 4µ 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.

When the chromatograms are recorded under the prescribed conditions the retention time of nabumetone is about 4 minutes.

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 for chromatography.

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.