Diazoxide

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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C₈H₇ClN₂O₂S 230.67

2H-1,2,4-Benzothiadiazine, 7-chloro-3-methyl-, 1,1-dioxide;

7-Chloro-3-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide    CAS RN®: 364-98-7.

1 DEFINITION

Diazoxide contains NLT 97.0% and NMT 102.0% of diazoxide (C₈H₇ClN₂O₂S), calculated on the dried basis.

2 IDENTIFICATION

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

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

3.1 Procedure

Buffer: Dissolve 1.56 g of sodium phosphate, monobasic in 1000 mL of water. Adjust with phosphoric acid to a pH of 2.5.

Mobile phase: Acetonitrile, methanol, and Buffer (10:10:80)

Diluent: Methanol and Buffer (50:50)

Standard solution: 0.05 mg/mL of USP Diazoxide RS in Diluent. Sonicate to dissolve if needed.

Sample solution: 0.05 mg/mL of Diazoxide in Diluent. Sonicate to dissolve if needed.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm × 5-cm; 2.6-µm packing L11
• Temperatures
• Autosampler: 10°
• Column: 30°
• Flow rate: 1 mL/min
• Injection volume: 20 µL
• Run time: NLT 2 times the retention time of diazoxide

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of diazoxide (C₈H₇ClN₂O₂S) in the portion of Diazoxide taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of diazoxide from the Sample solution

rₛ = peak response of diazoxide from the Standard solution

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

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

Acceptance criteria: 97.0%–102.0% on the dried basis

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.1%

Change to read:

4.2 Organic Impurities

Buffer and Diluent: Prepare as directed in the Assay.

Solution A: Methanol and Buffer (15:85)

Solution B: Acetonitrile and methanol (70:30)

Mobile phase: See Table 1.

Table 1

Sensitivity solution: 0.25 µg/mL of USP Diazoxide RS in Diluent from the Standard solution in the Assay

Standard solution: 0.5 µg/mL of USP Diazoxide RS in Diluent from the Standard solution in the Assay

Sample solution: 0.5 mg/mL of Diazoxide in Diluent. Sonication may be used to aid in dissolution.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 220 nm
• Column: 4.6-mm × 5-cm; 2.6-µm packing L11
• Temperatures
• Autosampler: 10°
• Column: 30°
• Flow rate: 0.8 mL/min
• Injection volume: 20 µL

System suitability

• Samples: Sensitivity solution and Standard solution
• Suitability requirements
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 5.0%, Standard solution
• Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentages of specified and unspecified impurities in the portion of Diazoxide taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵤ = peak response of specified and unspecified impurities from the Sample solution

rₛ = peak response of diazoxide from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

a 7-Chloro-2H-1,2,4- benzothiadiazin-3(4H)-one 1,1-dioxide.

5 SPECIFIC TESTS

5.1 Loss on Drying 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Diazoxide RS