Midodrine Hydrochloride

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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C₁₂H₁₈N₂O₄ · HCl 290.74

Acetamide, 2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]-, monohydrochloride, (±)-;

(±)-2-Amino-N-(β-hydroxy-2,5-dimethoxyphenethyl)acetamide monohydrochloride   CAS RN®: 3092-17-9.

1 DEFINITION

Midodrine Hydrochloride contains NLT 98.0% and NMT 102.0% of midodrine hydrochloride (C₁₂H₁₈N₂O₄ · HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

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

C. Identification Tests-General, Chloride 〈191〉: A 10 mg/mL solution of Midodrine Hydrochloride in water meets the requirements.

3 ASSAY

3.1 Procedure

Buffer: 13.6 g/L of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 4.00 ± 0.05.

Mobile phase: Acetonitrile and Buffer (3:22)

Standard solution: 0.05 mg/mL of USP Midodrine Hydrochloride RS in Mobile phase

Sample solution: 0.05 mg/mL of Midodrine Hydrochloride in Mobile phase

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 290 nm
• Column: 4.6-mm × 15-cm; 5-µm packing L1
• Flow rate: 1 mL/min
• Injection size: 20 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Column efficiency: NLT 3000 theoretical plates
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₂H₁₈N₂O₄ · HCl in the portion of Midodrine Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of midodrine from the Sample solution

rₛ = peak response of midodrine from the Standard solution

Cₛ = concentration of USP Midodrine Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Midodrine Hydrochloride in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.2%. A 1-g sample is used.

4.2 Organic Impurities

4.2.1 Procedure

Buffer and Mobile phase: Proceed as directed in the Assay.

Standard solution: 1.0 µg/mL of USP Midodrine Hydrochloride RS and 2.0 µg/mL of USP Midodrine Related Compound A RS in Mobile phase

Sample solution: 1.0 mg/mL of Midodrine Hydrochloride in Mobile phase

Chromatographic system: Proceed as directed in the Assay except for the following:

Injection size: 50 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Resolution: NLT 2.0 between midodrine hydrochloride and midodrine hydrochloride related compound A
• Tailing factor: NMT 2.0 for midodrine hydrochloride
• Relative standard deviation: NMT 2.0% for both midodrine hydrochloride and midodrine related compound A

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of midodrine related compound A in the portion of Midodrine Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of midodrine related compound A from the Sample solution

rₛ = peak response of midodrine related compound A from the Standard solution

Cₛ = concentration of USP Midodrine Related Compound A RS in the Standard solution (mg/mL)

Cᵤ = concentration of Midodrine Hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of any individual impurity in the portion of Midodrine Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of each impurity from the Sample solution

rₛ = peak response of midodrine from the Standard solution

Cₛ = concentration of USP Midodrine Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Midodrine Hydrochloride in the Sample solution (mg/mL)

Impurity Table 1

ᵃ 1-(2,5-Dimethoxyphenyl)-2-aminoethanol.

5 SPECIFIC TESTS

Water Determination, Method I 〈921〉: NMT 0.5%

pH 〈791〉: 4.0–5.0. Use 50 mg/mL of the midodrine hydrochloride sample.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers and store at room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Midodrine Hydrochloride RS

USP Midodrine Related Compound A RS

2-Amino-1-(2,5-Dimethoxyphenyl)ethanol.

C₁₀H₁₅NO₃ 197.23