- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Desmopressin Tablets |
Vasopressin analogue; treatment of diabetes insipidus; nocturnal enuresis; haemophillia; von Willebrand's disease.
Desmopressin Tablets contain Desmopressin.
The tablets comply with the requirements stated under Tablets and with the following requirements.
90.0 to 110.0% of the stated amount of the peptide.
In the test for Uniformity of content, the principal peak in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).
Comply with the dissolution test for tablets and capsules, Appendix XII B 1.
test conditions
(a) Use Apparatus 2, rotating the paddle at 75 revolutions per minute.
(b) Use 500 mL of water as the medium.
(c) After 45 minutes, withdraw a 20 mL sample of the medium and filter.
(d) Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Use the filtered dissolution medium.
(2) Prepare a solution of desmopressin EPCRS in water with a final concentration equal to that expected for solution (1).
The chromatographic procedure described under Uniformity of content may be used.
Calculate the total content of desmopressin C46H64N14O12S2, in the medium using the declared content of C46H64N14O12S2 in desmopressin EPCRS.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions and the normalisation procedure:
(1) Shake a quantity of powdered tablets containing 0.5 mg with 1 mL water to give a final concentration of 0.05% w/v of the peptide.
(2) Dissolve the contents of a vial of oxytocin/desmopressin validation mixture EPCRS in 0.5 mL of water.
(a) Use a stainless steel column (12 cm x 4.0 mm) packed with octadecylsilyl silica gel for chromatography (5 µm).
(b) Use linear 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 50 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.
The retention time of desmopressin is about 16 minutes and the retention time for 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.
In the chromatogram obtained with solution (1):
the area of any secondary peak is not more than 2.0%.
the total area of any such peaks is not more than 4.0%.
Disregard any peak due to the solvent or with a relative amount less than 0.05%.
Tablets containing less than 2 mg of Desmopressin comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions:
(1) Add sufficient water to one tablet to produce a solution containing 0.01% w/v of Desmopressin.
(2) 0.01% w/v of desmopressin EPCRS in water.
(a) Use a stainless steel column (12 cm x 4.0 mm) packed with octadecylsilyl silica gel for chromatography (5 µm).
(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 50 µL of each solution.
4 volumes of acetonitrile for chromatography and 6 volumes of 0.067m mixed phosphate buffer solution pH 7.0.
The retention time of desmopressin is about 5 minutes.
Calculate the content of C46H64N14O12S2 in each tablet from the chromatograms obtained and from the declared content of C46H64N14O12S2 in desmopressin EPCRS.
Use the average of the 10 individual results obtained in the test for Uniformity of content.
Desmopressin Tablets should be protected from moisture.