Desmopressin Intranasal Solution

Vasopressin analogue; treatment of diabetes insipidus; haemophillia; von Willebrand's disease.

Desmopressin Intranasal Solution is a solution of Desmopressin containing suitable buffering agents and preservatives.

The intranasal solution complies with the requirements stated under Nasal Preparations and with the following requirements.

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

A colourless solution.

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

pH, 3.5 to 5.5, Appendix V L.

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

(1) Dilute a volume of the intranasal solution in water to give a final concentration of 0.0025% w/v of the peptide.

(2) Dissolve the contents of a vial of oxytocin/desmopressin validation mixture EPCRS in 10 mL of water.

(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 200 µL of each solution.

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

Mobile phase B  10 volumes of acetonitrile for chromatography and 10 volumes of mobile phase A.

Using the prescribed conditions the retention time of desmopressin is about 16 minutes and the retention time of oxytocin is about 17 minutes.

The test is not valid unless, in the chromatogram obtained with solution (2), the resolution factor between the two principal peaks is at least 1.5;

the peak due to desmopressin is clearly separated from the peak due to the antimicrobial preservative stated on the label.

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%.

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

(1) Dilute a volume of the intranasal solution in water to give a final concentration of 0.0025% w/v of the peptide.

(2) 0.0025% w/v of desmopressin EPCRS in water.

(3) Dissolve the contents of a vial of oxytocin/desmopressin validation mixture EPCRS in 1 mL of water.

(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 2 mL per minute.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 220 nm.

(f) Inject 200 µL of each solution.

A mixture of 2 volumes of acetonitrile for chromatography and 8 volumes of 0.067m mixed phosphate buffer solution, pH 7.0.

The test is not valid unless:

in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 1.5.

the peak due to desmopressin is clearly separated from the peak due to the antimicrobial preservative stated on the label.

The retention time of desmopressin is about 5 minutes. If necessary adjust the concentration of acetonitrile in the mobile phase to obtain the correct retention time and resolution factor.

Calculate the content of C₄₆H₆₄N₁₄O₁₂S₂ in the intranasal solution from the chromatograms obtained and from the declared content of C₄₆H₆₄N₁₄O₁₂S₂ in desmopressin EPCRS.

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