Desmopressin Nasal Spray

(Ph. Eur. 11.6 update)

Action and use

Vasopressin analogue; treatment of diabetes insipidus.

DEFINITION

Desmopressin Nasal Spray is a solution of Desmopressin containing suitable buffering agents and preservatives in a suitable container.

The nasal spray complies with the requirements stated under Nasal Preparations and with the following requirements.

Content of desmopressin, C₄₆H₆₄N₁₄O₁₂S₂

90.0 to 110.0% of the stated amount of the peptide.

CHARACTERISTICS

A colourless solution.

IDENTIFICATION

In the Assay, the principal peak in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

TESTS

Acidity

pH, 3.5 to 5.5, Appendix V L.

Related substances

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

(1) If necessary dilute a volume of the nasal spray in a solution of 0.9% w/v of sodium chloride to produce a solution containing 0.01 to 0.015 % w/v of the peptide.

(2) Dissolve the contents of a vial of desmopressin impurity standard BPCRS in 1 mL of a solution of 0.9% w/v sodium chloride.

CHROMATOGRAPHIC CONDITIONS

(a) Use a stainless steel column (12 cm × 4.0 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Nucleosil C18 is suitable).

(b) Use gradient 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 220 nm.

(f) Inject 100 μL of each solution.

MOBILE PHASE

Mobile phase A 0.067M mixed phosphate buffer solution, pH 7.0.

Mobile phase B acetonitrile for chromatography

SYSTEM SUITABILITY

The test is not valid unless:

in the chromatogram obtained with solution (2), the resolution between the two principal peaks is at least 2.0;

the peak due to desmopressin is clearly separated from any peaks due to the excipients stated on the label.

LIMITS

In the chromatogram obtained with solution (1):

the area of any secondary peak is not more than 4.0%;

the total area of any such peaks is not more than 5.0%.

Disregard any peak due to the solvent, any antimicrobial preservative stated on the label and any peak with an area less than 0.3%.

ASSAY

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

(1) If necessary dilute a volume of the nasal spray in a solution of 0.9% w/v of sodium chloride to give a final
concentration in the range of 0.01 to 0.015 % w/v of the peptide.

(2) Dissolve the contents of a vial of desmopressin BPCRS in a solution of 0.9% sodium chloride to give a final concentration of 0.01% w/v of the peptide.

(3) Dissolve the contents of a vial of desmopressin impurity standard BPCRS in 1 mL of a solution of 0.9% w/v sodium chloride.

CHROMATOGRAPHIC CONDITIONS

(a) Use a stainless steel column (12 cm × 4.0 mm) packed with octadecylsilyl silica gel for chromatography (5 μm). (Nucleosil C18 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 220 nm.

(f) Inject 100 μL of each solution.

MOBILE PHASE

17 volumes of acetonitrile and 83 volumes of 0.067M mixed phosphate buffer solution, pH 7.0.

SYSTEM SUITABILITY

The test is not valid unless:

in the chromatogram obtained with solution (3), the resolution between the two principal peaks is at least 2.0;

the peak due to desmopressin is clearly separated from any peaks due to the excipients stated on the label.

DETERMINATION OF CONTENT

Calculate the content of C₄₆H₆₄N₁₄O₁₂S₂ in the nasal spray from the chromatograms obtained and from the declared content of C₄₆H₆₄N₁₄O₁₂S₂ in desmopressin BPCRS.

STORAGE

Desmopressin Nasal Spray should be protected from light and stored at a temperature of 2° to 8°, unless otherwise justified and authorised.

IMPURITIES

The impurities limited by the requirements of this monograph include those listed under Desmopressin.