Ceftriaxone for injection (Ceftriaxoni ad injectionem)


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The International Pharmacopoeia - Tenth Edition, 2020

Ceftriaxone for injection (Ceftriaxoni ad injectionem)

Ceftriaxone for injection (Ceftriaxoni ad injectionem)
Description. A white to almost white powder.

2017-01

Category. Antibacterial.

Storage. Ceftriaxone for injection should be stored in a tightly closed container. The reconstituted solution should be used immediately after preparation.

Labelling. The designation on the container of ceftriaxone for injection should state that the active ingredient is ceftriaxone sodium and the quantity should be indicated in terms of equivalent amount of ceftriaxone.

Additional information. Strengths in the current WHO Model List of Essential Medicines (EML): 250 mg, 1 g (as sodium salt) in vial. Strength in the current WHO EML for children: 250 mg, 1 g (as sodium salt) in vial.

The injection is reconstituted by dilution of Ceftriaxone for injection in Water for injections.

Requirements

The powder for injection and the reconstituted solution for injection comply with the monograph on Parenteral preparations.

Definition. Ceftriaxone for injection is a sterile powder containing Ceftriaxone sodium with or without excipients.

Ceftriaxone for injection contains not less than 90.0% and not more than 110.0% of the labelled amount of ceftriaxone (C18H18N8 O7S3).
Identity tests

· Either tests A and D or tests B, C and D may be applied.

A. Carry out the examination as described under 1.7 Spectrophotometry in the infrared region. The infrared absorption spectrum is concordant with the spectrum obtained from ceftriaxone sodium RS or with the reference spectrum of ceftriaxone sodium.

B. Carry out the test as described under 1.14.4 High-performance liquid chromatography using the conditions given under “Assay”. The retention time of the principal peak in the chromatogram obtained with solution (1) corresponds to the retention time of the ceftriaxone peak in the chromatogram obtained with solution (2).

C. Carry out the test as described under 1.14.1 Thin-layer chromatography using silica gel R6 as the coating substance and a mixture of 9 volumes of methanol R and 1 volume of water R. Apply separately to the plate 1µL of each of 2 solutions in water R containing (A) 4 mg of the test substance per mL and (B) 4 mg of ceftriaxone sodium RS per mL. After removing the plate from the chromatographic chamber allow it to dry in air and examine the chromatogram in ultraviolet light (254 nm). The principal spot obtained with solution (A) corresponds in position, appearance and intensity with that obtained with solution (B).

D. When tested for sodium as described under 2.1 General identification tests, yields the characteristic reaction.

Water. Determine as described under 2.8 Determination of water by the Karl Fischer method, method A, using about 0.100 g of the powder. The water content is not more than 110 mg per g.

Clarity and colour of solution. Dissolve 2.40 g in carbon-dioxide-free water R and dilute to 20.0 mL with the same solvent (solution A). Dilute 2 mL of solution A to 20 mL carbon-dioxide-free water R. The solution is clear and not more intensely coloured than reference solution YW2 when compared as described under 1.11.1 Colour of liquids. (Keep the remaining solution (solution A) for the “pH value”.)

pH value (1.13). pH of the solution prepared for the “Clarity and colour of solution” (solution A), 6.0–8.0.

Bacterial endotoxins. Carry out the test described under 3.4 Test for bacterial endotoxins; contains not more than 0.09 IU of endotoxin per mg of ceftriaxone.

Related substances

Carry out the test as described under 1.14.4 High-performance liquid chromatography using the conditions given under “Assay”.

Prepare the following solutions in mobile phase: for solution (1) dissolve about 30 mg of the powder and dilute to 100.0 mL. For solution (2) dilute 1 volume of solution (1) to 100 volumes. For solution (3) dissolve about 5 mg ceftriaxone sodium RS and about 5 mg of ceftriaxone impurity A RS and dilute to 100.0 mL.

Inject 20 µL of solution (3). The test is not valid unless the resolution factor between the peaks due to ceftriaxone and ceftriaxone impurity A is at least 3.0. Ceftriaxone impurity A is eluted at a relative retention of about 1.4 with reference to ceftriaxone

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The International Pharmacopoeia - Tenth Edition, 2020

Ceftriaxone for injection (Ceftriaxoni ad injectionem)

(retention time about 9 minutes).
Inject alternately 20 µL each of solutions (1) and (2). Record the chromatograms for about 2 times the retention time of ceftriaxone.
In the chromatogram obtained with solution (1):
-the area of any impurity peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%); -the sum of the areas of all impurity peaks is not greater than five times the area of the principal peak in the chromatogram obtained with solution (2) (5.0%). Disregard any peak with an area less than 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
Assay
Carry out the test as described under 1.14.4 High-performance liquid chromatography using a stainless steel column (25 cm x 4.6 mm) packed with particles of base-deactivated silica gel, the surface of which has been modified with chemically-bonded octadecylsilyl groups (5 µm).
As the mobile phase use a solution prepared as follows: dissolve 2.0 g of tetradecylammonium bromide R and 2.0 g of tetraheptylammonium bromide R in a mixture of 440 mL of water R, 55 mL of phosphate buffer, pH 7.0 (0.067 mol/L) TS, 5.0 mL of a citrate buffer pH 5.0 TS and 500 mL of acetonitrile R and filter.
Determine the weight of the contents of 10 containers. Prepare the following solutions in mobile phase. For solution (1) transfer a quantity of the mixed contents containing the equivalent of about 30 mg of ceftriaxone, accurately weighed, to a 100 mL volumetric flask, dissolve and dilute to volume. For solution (2) dissolve about 35 mg of ceftriaxone sodium RS, accurately weighed, and dilute to 100.0 mL. For solution (3) dissolve about 5 mg ceftriaxone sodium RS and 5 mg of ceftriaxone impurity A RS to 100.0 mL.
Operate with a flow rate of 1.5 mL per minute. As a detector use an ultraviolet spectrophotometer set at a wavelength of 254 nm.
Inject 20 µL of solution (3). The test is not valid unless the resolution factor between the peaks due to ceftriaxone and ceftriaxone impurity A is at least 3.0.
Inject alternately 20 µL each of solution (1) and (2). Measure the areas of the peaks corresponding to ceftriaxone and calculate the percentage content of ceftriaxone (C18H18N8O7S3) per container, using the declared content of C18H18N8Na2O7S3 in ceftriaxone sodium RS. Each mg of C18H18N8Na2O7S3 is equivalent to 0.9274 mg of C18H16N8O7S3. Impurities
The impurities limited by the requirements of this monograph include those listed in the monograph for Ceftriaxone sodium.

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Ceftriaxone for injection (Ceftriaxoni ad injectionem)