Fenoldopam Mesylate Injection

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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1 DEFINITION

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Fenoldopam Mesylate Injection is a sterile solution of fenoldopam mesylate (C₁₆H₁₆CINO₃·CH₄SO₃). It contains an amount of fenoldopam mesylate, equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of fenoldopam (C₁₆H₁₆CINO₃) (USP 1-Dec-2019)

2 IDENTIFICATION

Delete the following:

A. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Standard solution: 1 mg/mL in methanol

Sample solution: Pipet 1.0 mL of Injection into a 10-mL volumetric flask. Dilute to volume with methanol, and mix.

Application volume: 20 µL

Developing solvent system: Acetone, chloroform, acetic acid, and water (6:2:1:1)

Place the mixture in a paper-lined chromatographic chamber, and equilibrate for about 15 min before use.

Analysis: Proceed as directed in the chapter, and then dry the plate under a current of warm air until completely dry. Place the plate into a second chromatographic chamber containing iodine crystals, and examine the plate.

Acceptance criteria: Meets the requirements. (USP 1-Dec-2019)

Add the following:

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay (USP 1-Dec-2019)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

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3.1 PROCEDURE

Solution A: 1.38 g/L of monobasic sodium phosphate monohydrate and 1.88 g/L of sodium hexanesulfonate in water. Adjust with a 10% v/v phosphoric acid (USP 1-Dec-2019) solution to a pH of 2.5.

Mobile phase: Methanol and Solution A (33:67)

Diluent: 1.38 g/L of monobasic sodium phosphate monohydrate in water. Adjust with a 10% v/v phosphoric acid (USP 1-Dec-2019) solution to a pH of 2.5. (USP 1-Dec-2019)

Standard solution: 0.263 mg/mL of USP Fenoldopam Mesylate RS (USP 1-Dec-2019) in Diluent

Sample solution: Nominally 0.2 mg/mL of fenoldopam in Diluent from Injection (USP 1-Dec-2019)

3.2 Chromatographic system

(See Chromatography (621), System Suitability.) (USP 1-Dec-2019)

Mode: LC

Detector: UV 225 nm. For Identification A, use a diode array detector in the range of 200-400 nm. (USP 1-Dec-2019)

Column: 4.6-mm x 25-cm; 5-µm (USP 1-Dec-2019) packing L1

Column temperature: 33° (USP 1-Dec-2019)

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of fenoldopam (USP 1-Dec-2019)

3.3 System suitability

Sample: (USP 1-Dec-2019) Standard solution

Suitability requirements

(USP 1-Dec-2019)

Tailing factor: (USP 1-Dec-2019) NMT 2.0 for the fenoldopam peak

Relative standard deviation: NMT 2.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fenoldopam (USP 1-Dec-2019) (C₁₆H₁₆CINO₃ (USP 1-Dec-2019)) in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x 100

r_U = peak response of fenoldopam from the Sample solution

r_S = peak response of fenoldopam from the Standard solution s

C_S = concentration of USP Fenoldopam Mesylate RS in the Standard solution (mg/mL)

C_U= nominal concentration of fenoldopam in the Sample solution (mg/mL)

M_r1 = molecular weight of fenoldopam, 305.76

M_r2 = molecular weight of fenoldopam mesylate, 401.86

Acceptance criteria: 90.0%-110.0%

4 OTHER COMPONENTS

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CONTENT OF SODIUM METABISULFITE (if present) (USP 1-Dec-2019)

Sample: Transfer 10.0 mL of Injection to a glass -stoppered conical flask containing 5.0 mL of 0.1 N iodine VS, and swirl to dissolve. Allow to stand for exactly 5 min, protected from light.

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Endpoint detection: Visual (USP 1-Dec-2019)

CIAL s iodine w

Analysis: Add 0.5 mL of hydrochloric acid. Titrate the excess iodine with 0.05 N sodium thiosulfate VS until the solution is pale yellow. (USP 1-Dec-2019) Add 0.5 mL of starch TS as indicator and complete the titration to a colorless endpoint. (USP 1-Dec-2019) Perform a blank determination using 10 mL of water (USP 1-Dec-2019) and make any necessary correction. Each milliliter of 0.05 N sodium thiosulfate is equivalent to 2.3763 mg of sodium metabisulfite.

Acceptance criteria: NLT 0.25 mg/mL of Injection

5 IMPURITIES

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ORGANIC IMPURITIES

Solution A, Mobile phase, Diluent, (USP 1-Dec-2019) Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.263 mg/mL of USP Fenoldopam Mesylate RS and 0.274 µg/mL of USP Fenoldopam Related Compound B RS in Diluent (USP 1-Dec-2019)

System suitability

Sample: (USP 1-Dec-2019) Standard solution

Suitability requirements

Tailing factor: NMT 2.5 for the fenoldopam related compound B peak; (USP 1-Dec-2019) NMT 2.0 for the fenoldopam peak

Relative standard deviation: NMT 2.0% for the fenoldopam related compound B and fenoldopam peaks (USP 1-Dec-2019)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fenoldopam related compound Bfree base (USP 1-Dec-2019) in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x 100

r_U = peak response of fenoldopam related compound B from the Sample solution

r_S = peak response of fenoldopam related compound B from the Standard solution

C_S = concentration of USP Fenoldopam Related Compound B RS in the Standard solution (mg/mL)

C_U = nominal concentration of fenoldopam in the Sample solution (mg/mL)

M_r1 = molecular weight of fenoldopam related compound B free base, 271.32

M_r2 = molecular weight of fenoldopam related compound B, 367.42 (USP 1-Dec-2019)

Acceptance criteria: NMT 0.6%

6 SPECIFIC TESTS

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6.1 BACTERIAL ENDOTOXINS TEST (85)

Meets the requirements (USP 1-Dec-2019)

6.2 STERILITY TESTS (71)

Meets the requirements

6.3 PARTICULATE MATTER IN INJECTIONS (788)

Meets the requirements for small-volume injections

6.4 PH (791)

2.8-3.8

6.5 OTHER REQUIREMENTS

Meets the requirements under Injections and Implanted Drug Products (1).

7 ADDITIONAL REQUIREMENTS

7.1 PACKAGING AND STORAGE

Preserve as described in Packaging and Storage Requirements (659), Injection Packaging, preferably of Type I glass. Store in a refrigerator or at controlled room temperature.

Change to read:

7.2 USP REFERENCE STANDARDS (11)

USP Fenoldopam Mesylate RS

USP Fenoldopam Related Compound B RS

1H-3-Benzazepine-7,8-diol, 2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-, methanesulfonate (salt);

Also known as

1-(4-Hydroxyphenyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine-7,8-diol methanesulfonate.

C₁₆H₁₇NO₃·CH₄SO₃ 367.42 (USP 1-Dec-2019)