Minoxidil

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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C H N O 209.25

2,4-Pyrimidinediamine, 6-(1-piperidinyl)-, 3-oxide;

2,4-Diamino-6-piperidinopyrimidine 3-oxide CAS RN: 38304-91-5; UNII: 5965120SH1.

DEFINITION

Minoxidil contains NLT 97.0% and NMT 103.0% of minoxidil (C₉H₁₅N₅O), calculated on the dried basis.

IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared SpectroscoRX _{(CN 1-MAY-2020)}: [NOTE-Methods described in 197A or 197M may be used.] _{(USP 1-May-2020)} Do not dry specimens.

Add the following:

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

_{(USP 1-May-2020)}

1 ASSAY

Change to read:

PROCEDURE

Mobile phase: Methanol, glacial acetic acid, and water (70:1:30). Add 3.0 g/L of Docusate sodium. Adjust with perchloric acid to a pH of 3.0.

_{(USP 1-May-2020)}

Standard solution: 0.25 mg/mL of USP Minoxidil RS in Mobile phase _{(USP 1-May-2020)}

Sample solution: 0.25 mg/mL of Minoxidil in Mobile phase _{(USP 1-May-2020)}

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm x 25-cm; 5-µm _{(USP 1-May-2020)} packing 11

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of the minoxidil peak _{(USP 1-May-2020)}

System suitability

Sample: Standard solution _{(USP 1-May-2020)}

Suitability requirements

Tailing factor: NMT 2.0 _{(USP 1-May-2020)}

Relative standard deviation: NMT 1.10% _{(USP 1-May-2020)}

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of minoxidil (C₉H₁₅N₅O) in the portion of Minoxidil taken:

Result = (r_u /r_s ) _{(USP 1-May-2020)} × (C_s /C_u ) × 100

r _{(USP 1-May-2020)} = peak response of minoxidil _{(USP 1-May-2020)} from the Sample solution

r _{(USP 1-May-2020)} = peak response of minoxidil _{(USP 1-May-2020)} from the Standard solution

C = concentration of USP Minoxidil RS in (USP 1-May-2020) the Standard solution (mg/mL)

C = concentration of Minoxidil in _{(USP 1-May-2020)} the Sample solution (mg/mL)

Acceptance criteria: 97.0%–103.0% on the dried basis

2 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.5%

Change to read:

ORGANIC IMPURITIES

Mobile phase: Dissolve 2.0 g of sodium lauryl sulfate in a mixture of 600 ml of methanol, 10 ml of glacial acetic acid, and 400 mL of water.

Adjust with perchloric acid to a pH of 3.0 ± 0.1.

Diluent: Methanol and water (50:50)

Standard solution: 0.005 mg/mL of USP Minoxidil RS in Diluent

Sensitivity solution: 0.125 µg/mL of USP Minoxidil RS in Diluent from the Standard solution

Sample solution: 0.25 mg/mL of Minoxidil in Diluent prepared as follows. Transfer a suitable amount of Minoxidil in an appropriate volumetric flask. Initially add Diluent to about 60% of the flask volume, shake on a mechanical shaker for 20 min, and then dilute with Diluent to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.9-mm x 15-cm; 4-µm packing 11

Flow rate: 0.5 mL/min

Injection volume: 40 µL

Run time: NLT 3 times the retention time of the minoxidil peak

System suitability

Samples: Standard solution and Sensitivity solution

Suitability requirements

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of the Minoxidil taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of minoxidil from the Standard solution

C_s = concentration of USP Minoxidil RS in the Standard solution (mg/mL)

C_u = concentration of Minoxidil in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

^a 4-Chloropyrimidine-2,6-diamine-1-oxide.

^b 6-Chloropyrimidine-2,4-diamine.

^c 6-(Piperidin-1-yl)pyrimidine-2,4-diamine.

3 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 50° and at a pressure not exceeding 5 mm of mercury for 3 h.

Acceptance criteria: NMT 0.5%

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Minoxidil RS