31/5/2019 Clotrimazole Pessaries - British Pharmacopoeia

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Clotrimazole Pessaries

General Notices

Action and use

Antifungal.

DEFINITION

Clotrimazole Pessaries are moulded pessaries containing Clotrimazole.

The Pessaries comply with the requirements stated under Vaginal Preparations and with the following requirements.

Content of clotrimazole, C22H17ClN2

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) Shake a quantity of the pessaries, cut into small pieces, containing 20 mg of Clotrimazole with 4 mL of dichloromethane for 30 minutes, centrifuge and
use the supernatant liquid.
(2) 0.5% w/v of clotrimazole BPCRS in dichloromethane.

CHROMATOGRAPHIC CONDITIONS

(a) Use a silica gel precoated plate (Merck silica gel 60 plates are suitable).
(b) Use the mobile phase as described below in a chromatography tank containing 25 mL of 13.5M ammonia in a beaker.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in a current of air and spray with dilute potassium iodobismuthate solution.

MOBILE PHASE

di-isopropyl ether.

CONFIRMATION

The principal spot in the chromatogram obtained with solution (1) is reddish brown and corresponds to the principal spot in the chromatogram obtained
with solution (2).

B. In the Assay, the chromatogram obtained with solution (1) shows a principal peak with the same retention time as the principal 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) Cut a suitable amount of pessaries into small pieces. Add 50 mL of methanol to a quantity of the pessaries containing 0.1 g of Clotrimazole and shake
for 20 minutes. Dilute to 100 mL with methanol and filter. To 20 mL of the filtrate add 50 mL of methanol and sufficient water to produce 100 mL.
(2) 0.0002% w/v of 2-chlorotritanol BPCRS in a mixture of 3 volumes of water and 7 volumes of methanol.
(3) Dilute 1 volume of solution (1) to 50 volumes with a mixture of 3 volumes of water and 7 volumes of methanol.
(4) Dilute 1 volume of solution (3) to 40 volumes with a mixture of 3 volumes of water and 7 volumes of methanol.

CHROMATOGRAPHIC CONDITIONS

(a) Use a stainless steel column (20 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Lichrosorb RP-18 or Spherisorb ODS
1 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 215 nm.
(f) Inject 20 µL of each solution.
(g) For solution (1), allow the chromatography to proceed for 1.5 times the retention time of the principal peak.

MOBILE PHASE

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31/5/2019 Clotrimazole Pessaries - British Pharmacopoeia

30 volumes of 0.02M orthophosphoric acid and 70 volumes of methanol, adjust the pH of the mixture to 7.5 with a 10% v/v solution of triethylamine in
methanol.

SYSTEM SUITABILITY

The column efficiency, determined using the principal peak in the chromatogram obtained with solution (3), should be at least 9000 theoretical plates per
metre.

LIMITS

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).

Disregard any peak with an area less than the principal peak in the chromatogram obtained with solution (4) (0.05%).

ASSAY

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

(1) Weigh 20 pessaries and cut into small pieces. To a quantity of the pessaries containing 0.1 g of Clotrimazole add 50 mL of methanol and shake for 20
minutes. Dilute to 250 mL with methanol, filter and to 10 mL of the filtrate add 60 mL of methanol and sufficient water to produce 100 mL.
(2) Dissolve 20 mg of clotrimazole BPCRS in 70 mL of methanol, add sufficient water to produce 100 mL and dilute 1 volume of the resulting solution to 5
volumes with a mixture of 30 volumes of water and 70 volumes of methanol.

CHROMATOGRAPHIC CONDITIONS

The chromatographic conditions described under Related substances may be used.

SYSTEM SUITABILITY

The column efficiency, determined using the peak in the chromatogram obtained with solution (2), should be at least 9000 theoretical plates per metre.

DETERMINATION OF CONTENT

Calculate the content of C22H17ClN2 in the pessaries from the chromatograms obtained and using the declared content of C22H17ClN2 in clotrimazole

BPCRS.

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