Streptomycin Injection

Action and use

Aminoglycoside antibacterial; antituberculosis drug.

Definition

Streptomycin Injection is a sterile solution of Streptomycin Sulfate in Water for Injections. It is either supplied as a ready-to-use solution or it is prepared by dissolving Streptomycin Sulfate for Injection in Water for Injections.

The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.

Characteristics

A colourless to yellow solution.

Bacterial endotoxins

Carry out the test for bacterial endotoxins, Appendix XIV C. Dilute the injection, if necessary, with water BET to give a solution containing the equivalent of 10 mg of streptomycin per mL (solution A). The endotoxin limit concentration of solution A is 2.5 IU per mL.

Storage

Streptomycin Injection prepared by dissolving the contents of a sealed container in Water for Injections should be used immediately after preparation but, in any case, within the period recommended by the manufacturer when prepared and stored strictly in accordance with the manufacturer’s instructions.

Labelling

The strength is stated in terms of the equivalent amount of streptomycin in a suitable dose-volume.

When supplied as a ready-to-use solution, the injection also complies with the following requirements.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Dilute a suitable volume of the injection with sufficient water to produce a solution containing the equivalent of 0.08% w/v of streptomycin.

(2) 0.1% w/v of streptomycin sulfate EPCRS in water.

(3) 0.1% w/v of streptomycin sulfate EPCRS, 0.1% w/v of neomycin sulfate EPCRS and 0.1% w/v of kanamycin monosulfate BPCRS in water.

chromatographic conditions

(a) Use a plate prepared in the following manner. Mix 0.3 g of carbomer (Carbopol 934 is suitable) with 240 mL of water, allow to stand with moderate shaking for 1 hour, adjust to pH 7 by the gradual addition, with constant shaking, of 2m sodium hydroxide and add 30 g of silica gel H. Spread a uniform layer of the resulting suspension, 0.75 mm thick. Heat the plate at 110° for 1 hour, allow to cool and use immediately.

(b) Use the mobile phase as described below.

(d) Develop the plate to 12 cm.

(e) After removal of the plate, dry it in a current of warm air, spray with a mixture of equal volumes of a 0.2% w/v solution of naphthalene-1,3-diol in ethanol (96%) and a 46% w/v solution of sulfuric acid and heat at 150° for 5 to 10 minutes.

mobile phase

A 7% w/v solution of potassium dihydrogen orthophosphate.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) shows three clearly separated principal spots.

confirmation

The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

B. Mix 0.05 mL with 4 mL of water, add 1 mL of 1m sodium hydroxide and heat in a water bath for 4 minutes. Add a slight excess of hydrochloric acid and 0.1 mL of iron(iii) chloride solution R1. A violet colour is produced.

Tests

Acidity

pH, 5.0 to 6.5, Appendix V L.

Streptomycin B

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Dilute a volume of the injection containing the equivalent of 0.16 g of streptomycin in sufficient of a freshly prepared mixture of 3 volumes of sulfuric acid and 97 volumes of methanol to produce 5 mL, heat under a reflux condenser for 1 hour, cool, rinse the condenser with methanol and add sufficient methanol to produce 20 mL (1% w/v solution).

(2) Dissolve 36 mg of d-mannose in sufficient of a freshly prepared mixture of 3 volumes of sulfuric acid and 97 volumes of methanol to produce 5 mL, heat under a reflux condenser for 1 hour, cool, rinse the condenser with methanol and add sufficient methanol to produce 50 mL. Dilute 5 mL of the resulting solution to 50 mL with methanol; this solution contains the equivalent of 0.03% w/v of streptomycin B (1 mg of d-mannose is equivalent to 4.13 mg of streptomycin B).

chromatographic conditions

(a) Use as the coating silica gel G.

(b) Use the mobile phase as described below.

(d) Develop the plate to 13 to 15 cm.

(e) After removal of the plate, allow it to dry in air and spray with a freshly prepared mixture of equal volumes of a 0.2% w/v solution of naphthalene-1,3-diol in ethanol (96%) and a 20% v/v solution of sulfuric acid and heat at 110° for 5 minutes.

mobile phase

25 volumes of glacial acetic acid, 25 volumes of methanol and 50 volumes of toluene.

limit

Any spot corresponding to streptomycin B in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (3%).

Assay

Dilute a quantity containing the equivalent of 0.33 g of streptomycin to 100 mL with water for injections and carry out the microbiological assay of antibiotics, Appendix XIV A. The precision of the assay is such that the fiducial limits of error are not less than 95% and not more than 105% of the estimated potency.

Calculate the content of streptomycin in the injection, taking each 1000 IU found to be equivalent to 1 mg of streptomycin. The upper fiducial limit of error is not less than 97.0% and the lower fiducial limit of error is not more than 110.0% of the stated content.

Storage

Streptomycin Injection should be protected from light and stored at a temperature of 2° to 8°.

STREPTOMYCIN SULFATE FOR INJECTION

Streptomycin Sulphate for Injection

Definition

Streptomycin Sulfate for Injection is a sterile material consisting of Streptomycin Sulfate with or without excipients. It is supplied in a sealed container.

The contents of the sealed container comply with the requirements for Powders for Injections or Infusions stated under Parenteral Preparations and with the following requirements.

Identification

A. Comply with test A for Identification described in the requirements for the ready-to-use solution but using as solution (1) a solution prepared by dissolving a quantity of the contents of the sealed container in sufficient water to produce a solution containing the equivalent of 0.08% w/v of streptomycin.

B. Dissolve 5 to 10 mg in 4 mL of water and add 1 mL of 1m sodium hydroxide. Heat in a water bath for 4 minutes. Add a slight excess of 2m hydrochloric acid and 0.1 mL of iron(iii) chloride solution R1. A violet colour develops.

C. Yield the reactions characteristic of sulfates, Appendix VI.

Tests

Acidity or alkalinity

pH of a solution containing the equivalent of 25% w/v of streptomycin, 4.5 to 7.0, Appendix V L.

Streptomycin B

Comply with the test described in the requirements for the ready-to-use solution but using as solution (1) a solution prepared in the following manner. Dissolve a quantity containing the equivalent of 0.16 g of streptomycin in sufficient of a freshly prepared mixture of 3 volumes of sulfuric acid and 97 volumes of methanol to produce 5 mL, heat under a reflux condenser for 1 hour, cool, rinse the condenser with methanol and add sufficient methanol to produce 20 mL (1% w/v solution).

Loss on drying

When dried over phosphorus pentoxide at 60° at a pressure not exceeding 0.1 kPa for 24 hours, lose not more than 7.0% of their weight. Use 1 g.

Assay

Determine the weight of the contents of 10 containers as described in the test for uniformity of weight, Appendix XII C1, Powders for Parenteral Administration.

Dissolve a quantity of the mixed contents of the 10 containers containing the equivalent of 0.33 g of streptomycin in sufficient water for injections to produce 100 mL and carry out the microbiological assay of antibiotics, Appendix XIV A. The precision of the assay is such that the fiducial limits of error are not less than 95% and not more than 105% of the estimated potency. Calculate the content of streptomycin in the injection, taking each 1000 IU found to be equivalent to 1 mg of streptomycin. For a container of average content weight, the upper fiducial limit of error is not less than 95.0% and the lower fiducial limit of error is not more than 115.0% of the stated content.

Labelling

The label of the sealed container states the quantity of streptomycin sulfate contained in it in terms of the equivalent amount of streptomycin.