Diethylcarbamazine Citrate

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

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

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C₁₀H₂₁NO₃ · C₆H₈O₇             391.42

1-Piperazinecarboxamide, N,N-diethyl-4-methyl-, 2-hydroxy-1,2,3-propanetricarboxylate;

N,N-Diethyl-4-methyl-1-piperazinecarboxamide citrate (1:1) CAS RN^®: 1642-54-2; UNII: OS1Z389K8S.

1 DEFINITION

Diethylcarbamazine Citrate contains NLT 98.0% and NMT 102.0% of diethylcarbamazine citrate (C₁₀H₂₁NO₃ · C₆H₈O₇), calculated on the anhydrous basis. 

2 IDENTIFICATION

Add the following:

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{▲(USP 1-Aug-2020)}

Change to read:

B. _{▲(USP 1-AUG-2020)} IDENTIFICATION-ORGANIC NITROGENOUS BASES (181): Meets the requirements

Change to read:

C. _{▲(USP 1-AUG-2020)} IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests, Citrate: Meets the requirements

3 ASSAY

Change to read:

3.1 PROCEDURE

Solution A: 10 mg/mL of monobasic potassium phosphate in water

Solution B: 31.24 mg/mL of monobasic potassium phosphate in water

Mobile phase: Methanol and Solution A (10:90)

Standard solution: 0.1 mg/mL of USP Diethylcarbamazine Citrate RS in Solution B

Sample solution: 0.1 mg/mL of Diethylcarbamazine Citrate in Solution B

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 3.9-mm x 15-cm; 5-µm packing 11

Flow rate: 0.8 mL/min

Injection volume: 20 µL

3.1.2 System suitability

Sample: Standard solution

3.1.3 Suitability requirements

Relative standard deviation: NMT 2.0% ^▲_{▲(USP 1-Aug-2020)}

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of diethylcarbamazine citrate (C₁₀H₂₁NO₃ · C₆H₈O₇) in the portion of Diethylcarbamazine Citrate taken:

                Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution S

C_S = concentration of USP Diethylcarbamazine Citrate RS in the Standard solution (mg/mL)

C_U = concentration of Diethylcarbamazine Citrate in the Sample solution (mg/mL) 

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

4.1 Delete the following:

4.1.1 ORDINARY IMPURITIES (466).

Standard solution: Methanol

Sample solution: Methanol

Eluant: Methanol and ammonium hydroxide (100:1.5)

Visualization: 16 (USP 1-Aug-2020)

4.2 Add the following:

4.2.1 ORGANIC IMPURITIES, PROCEDURE 1

Impurity solution A: 0.1 mg/mL of 1-methylpiperazine in methanol

Impurity solution B: 0.1 mg/mL of 1,4-dimethylpiperazine in methanol

Standard solution: 50 mg/mL of USP Diethylcarbamazine Citrate RS in methanol

Sample solution: 50 mg/mL of Diethylcarbamazine Citrate in methanol

4.2.1.1 Chromatographic system

(See Chromatography (621), General Procedures. Thin-Layer Chromatograpby.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Developing solvent system: Ammonia solution, methyl ethyl ketone, and methanol (5:30:65)

4.2.1.2 Analysis

Samples: Impurity solution A, Impurity solution B, Standard solution, and Sample solution

Apply the Samples to a suitable thin-layer chromatographic plate. Develop the chromatograms in the Developing solvent system until the solvent front has moved two-thirds of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow the solvent to evaporate at about 100°-105°. Expose the plate to iodine vapor for about 30 min.

Determine the percentages of each impurity by comparing the intensity of the impurity spots within the Sample solution to those of the main spots from Impurity solution A and Impurity solution B, ignoring any impurity peak less intense than the main spots found in the Impurity solution A and Impurity solution B lanes.

Acceptance criteria: See Table 1.

Table 1

4.3 Change to read:

4.3.1 ORGANIC IMPURITIES, PROCEDURE 2

Solution A, Solution B, Mobile phase, and Chromatographic system: Proceed as directed in the Assay.

Citric acid solution: 1 mg/mL of citric acid in Solution BA _{▲(USP 1-Aug-2020)}

Standard solution: 0.003 mg/mL of USP Diethylcarbamazine Citrate RS in Solution B

Sample solution: 3 mg/mL of Diethylcarbamazine Citrate in Solution B. Filter or centrifuge, and use the clear filtrate or supernatant.

Analysis

Samples: Citric acid solution._{▲USP 1-Aug-2020)} Standard solution, and Sample solution

Calculate the percentage of each individual impurity in the portion of Diethylcarbamazine Citrate taken:

                Result = (r_U/r_S) x (C_S/C_U) × 100

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

r_S = peak response of diethylcarbamazine citrate from the Standard solution

C_S = concentration of USP Diethylcarbamazine Citrate RS in the Standard solution (mg/mL) S

C_U = concentration of Diethylcarbamazine Citrate in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard any peak having a retention time corresponding to that of the main peak from the Citric acid solution and any peak below 0.05%.

Table 2

(USP 1-Aug-2020)

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method /: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Diethylcarbamazine Citrate RS