Apomorphine Hydrochloride

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

C₁₇H₁₇NO₂ . HCI 1/2H₂O  312.79

C₁₇H₁₇NO₂ . HCI   303.79

4H-Dibenzo[de,g]quinoline-10,11-diol, 5,6,6a, 7-tetrahydro-6-methyl-, hydrochloride, hemihydrate, (R)-;

6aß-Aporphine-10,11-diol hydrochloride hemihydrate CAS RN®: 41372-20-7; UNII: F39049Y068.

Anhydrous CAS RN^®: 314-19-2; UNII: 9K13MD7A0D.

1 DEFINITION

Apomorphine Hydrochloride contains NLT 98.5% and NMT 101.5% of apomorphine hydrochloride (C₁₇H₁₇NO₂ . HCI), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

2.1 A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

2.2 B. IDENTIFICATION TESTS-GENERAL, Chloride (191)

Sample solution: 10 mg/mL of Apomorphine Hydrochloride in carbon dioxide-free water

Analysis: To 2 mL of the Sample solution add 0.1 mL of nitric acid. Mix, filter, and use the filtrate.

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Sample solution: Dissolve 250 mg of Apomorphine Hydrochloride in a mixture of 5.0 mL of 0.01 N hydrochloric acid and 50 mL of alcohol.

Analysis: Titrate the Sample solution with 0.1 N sodium hydroxide VS. Read the volume added between the first two points of inflexion. Each mL of 0.1 N sodium hydroxide is equivalent to 30.38 mg of apomorphine hydrochloride (C₁₇H₁₇NO₂ . HCI).

Acceptance criteria: 98.5%-101.5% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.1%

4.2 ORGANIC IMPURITIES

Diluent: Glacial acetic acid and water (1:99)

Solution A: 1.1-g/L solution of sodium octanesulfonate, adjusted with diluted phosphoric acid (1:1) to a pH of 2.2

Solution B: Acetonitrile

Mobile phase: See Table 1.

Return to original conditions and re-equilibrate the system.

System suitability solution: 0.25 mg/mL each of USP Apomorphine Hydrochloride RS and boldine in Diluent. [NOTE-Boldine is 2,9-dihydroxy-1,10-dimethoxyaporphine.]

Standard solution: 2.5 µg/mL of USP Apomorphine Hydrochloride RS in Diluent

Sensitivity solution: 0.14 µg/mL of USP Apomorphine Hydrochloride RS in Diluent from the Standard solution. [NOTE-The peak response of this solution is equivalent to that of a solution containing 1.25 µg/mL of morphine hydrochloride, taking into account the relative response factor of this impurity (see Table 2).]

Sample solution: 2.5 mg/mL of Apomorphine Hydrochloride in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 15-cm; 5-µm end-capped packing L1

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Sensitivity solution

[NOTE-The typical relative retention times for boldine and apomorphine are about 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.5 between boldine and apomorphine, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Apomorphine Hydrochloride taken: Result = (r_U/r_S) × (C_S/C_U) × (1/F) x 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of apomorphine from the Standard solution

C_S = concentration of USP Apomorphine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Apomorphine Hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard any peak below 0.05%.

Table 2

5 SPECIFIC TESTS

5.1 OPTICAL ROTATION, Specific Rotation (781S).

Sample solution: 10 mg/mL in Diluent

Diluent: 2.06-g/L solution of hydrochloric acid in water

Acceptance criteria: 48° to 52°, determined at 20°

5.2 LOSS ON DRYING (731).

Analysis: Dry a sample at 105° for 2 h.

Acceptance criteria: 2.0%-4.2%

5.3 COLOR OF SOLUTION

Sample solution: Place 100 mg of Apomorphine Hydrochloride in a suitable test tube, add 10 mL of cold, oxygen-free water, and agitate gently until dissolved.

Standard solution: Dissolve 5 mg of Apomorphine Hydrochloride in 100.0 mL of water. Transfer 1.0 mL of this solution to a test tube of the same size as that used for the Sample solution. Dilute with 6 mL of water, add 1 mL of a 50-mg/mL sodium bicarbonate solution, and then add 0.50 mL of iodine TS. Allow to stand for 30 s, add 0.60 mL of a 25-mg/mL sodium thiosulfate solution, and dilute with water to 10 mL.

Acceptance criteria: The color of the Sample solution, observed promptly after the Apomorphine Hydrochloride has dissolved, is not more intense than that of a color of the Standard solution.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.

USP REFERENCE STANDARDS (11)

USP Apomorphine Hydrochloride RS