Desmopressin Acetate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₄₆H₆₄N₁₄O₁₂S₂ · xC₂H₄O₂ · yH₂O 1069.22 (anhydrous, free base)

Vasopressin, 1-(3-mercaptopropanoic acid)-8-d-arginine-, acetate (salt) hydrate;

1-(3-Mercaptopropionic acid)-8-d-arginine-vasopressin, acetate (salt) hydrate.

x(acetate), y(water).

Monoacetate trihydrate CAS RN®: 62357-86-2; UNII: XB13HYU18U.

Monoacetate anhydrous CAS RN®: 62288-83-9; UNII: 1K12647SFC.

1 DEFINITION

Desmopressin Acetate is a synthetic octapeptide hormone having the property of antidiuresis. It is a synthetic analog of Vasopressin. It contains NLT 95.0% and NMT 105.0% of desmopressin (C₄₆H₆₄N₁₄O₁₂S₂), calculated on the anhydrous, acetic acid-free basis.

2 IDENTIFICATION

2.1 A. The monoisotopic mass by Mass Spectrometry 〈736〉 is 1068.4 ± 0.5 mass units.

2.2 B.

Buffer solution, Mobile phase, Standard solution, and Sample solution: Prepare as directed in the Assay.

Identity sample solution: 10 µg/mL each of USP Desmopressin Acetate RS and Desmopressin Acetate in Mobile phase

Acceptance criteria: The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. The major peaks of the Identity sample solution coelute.

3 ASSAY

Change to read:

3.1 Procedure

Buffer solution: Dissolve 3.4 g of monobasic potassium phosphate and 2.0 g of sodium 1-heptanesulfonic acid in 1000 mL of water. Adjust with phosphoric acid or sodium hydroxide to a pH of 4.50 ± 0.05, as needed. Pass through a filter of 0.45-µm pore size.

Mobile phase: Mix acetonitrile and Buffer solution (22:78), and degas. Make adjustments, if necessary (see Chromatography (621). System Suitability). [NOTE-The retention time of desmopressin is very sensitive to the composition of the Mobile phase.]

Standard solution: 20 µg/mL of USP Desmopressin Acetate RS in Mobile phase

Sample solution: 20 µg/mL of Desmopressin Acetate in Mobile phase

System suitability solution: Dissolve about 1 mg of USP Oxytocin Identification RS. accurately weighed, in a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. Transfer 5.0 mL each of the resulting solution and the Sample solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Chromatographic system

• (See Chromatography (621), System Suitability.)
• Mode: LC
• Detector: UV 220 nm
• Column: 4.6-mm x 25-cm; 5-µm packing 11
• Column temperature: 30^o
• Flow rate: 1.0 mL/min
• Injection volume: 50 µL

System suitability

• Samples: Standard solution and System suitability solution
• Suitability requirements
• Resolution: NLT 1.5 between desmopressin and oxytocin, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 2.0% for the desmopressin peak area for replicate injections, Standard solution
• Chromatogram similarity: The desmopressin peak elutes before the oxytocin peak, System suitability solution.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of desmopressin (C₄₆H₆₄N₁₄O₁₂S₂) in the portion of Desmopressin Acetate taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Desmopressin Acetate RS (calculated on the anhydrous, acetic acid-free basis) in the Standard solution (mg/ml.)

C_u = concentration of Desmopressin Acetate (calculated on the anhydrous, acetic acid-free basis) in the Sample solution (mg/mL)

Acceptance criteria: 95.0%-105.0% on the anhydrous, acetic acid-free basis

4 IMPURITIES

4.1 DESMOPRESSIN-RELATED IMPURITIES

Mobile phase and System suitability solution: Prepare as directed in the Assay.

Standard solution: 1 µg/mL of USP Desmopressin Acetate RS in Mobile phase, prepared by diluting 0.5 mL of the Standard solution from the Assay with Mobile phase to 10 mL

Sample solution: 200 µg/mL of Desmopressin Acetate in Mobile phase

Chromatographic system

• (See Chromatography (621), System Suitability.)
• Mode: LC
• Detector: UV 220 nm
• Column: 4.6-mm x 25-cm; 5-µm packing 11
• Column temperature: 30°
• Flow rate: 1.0 mL/min
• Injection volume: 200 µL

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 1.5 between desmopressin and oxytocin, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 5.0% for the desmopressin peak area for replicate injections, Standard solution
• Chromatogram similarity: The desmopressin peak elutes before the oxytocin peak, System suitability solution.

Analysis

Samples: Standard solution and Sample solution

Record the chromatograms, and measure the response for each peak, except for the main desmopressin peak of the Sample solution.

Calculate the percentage of each individual impurity in the portion of Desmopressin Acetate taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of each individual impurity from the Sample solution

r_s = peak response of desmopressin from the Standard solution

C_s = concentration of USP Desmopressin Acetate RS (calculated on the anhydrous, acetic acid-free basis) in the Standard solution (mg/mL)

C_u = concentration of Desmopressin Acetate (calculated on the anhydrous, acetic acid-free basis) in the Sample solution (mg/mL)

Acceptance criteria

• Any individual impurity: NMT 0.5%
• Total impurities: NMT 1.5%

5 OTHER COMPONENTS

ACETIC ACID IN PEPTIDES (503): 3.0%-8.0%

6 SPECIFIC TESTS

MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIC MICROORGANISMS (62): The total aerobic microbial count does not exceed 102 cfu/g.

WATER DETERMINATION (921), Method I, Method Ic: NMT 6.0%

BACTERIAL ENDOTOXINS TEST (85): The level of bacterial endotoxins is such that the requirement under the relevant dosage form monograph(s) in which Desmopressin Acetate is used can be met. Where the label states Desmopressin Acetate must be subjected to further processing during the preparation of injectable dosage forms, the level of bacterial endotoxins is such that the requirement under the relevant dosage form monograph(s) in which Desmopressin Acetate is used can be met.

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, preferably of Type I glass, protected from light and moisture. Store at a temperature not exceeding 25°, preferably between 2° and 8°.

Change to read

USP Reference Standards 〈11〉

USP Desmopressin Acetate RS

USP Oxytocin Identification RS