Doxazosin Mesylate

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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C₂₃H₂₅N₅O₅ · CH₄O₃S             547.58

Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-[(2,3-dihydro-1,4-benzodioxin-2-yl)carbonyl]-, monomethanesulfonate;1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl)piperazine monomethanesulfonate CAS RN: 77883-43-3; UNII:86P6PQK0MU.

1 DEFINITION

Doxazosin Mesylate contains NLT 98.0% and NMT 102.0% of doxazosin mesylate (C₂₃H₂₅N₅O₅ · CH₄O₃S), calculated on the dried 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.

3 ASSAY

PROCEDURE

Solution A: 50 mg/mL (w/v) of phosphoric acid in water

Solution B: Acetonitrile

Solution C: Water

Solution D: Mix 100 mL of Solution B and 2 g of phosphoric acid.

Mobile phase: See Table 1.

Table 1^a

^a Between sample injections, the system is re-equilibrated for at least 7 min or until a stable baseline is obtained, representing the starting composition.

System suitability solution: 12 µg/ml. of USP Doxazosin Related Compound A RS and 12 µg/mL of USP Doxazosin Related Compound B RS in a mixture of Solution C and Solution D (9:1), Initially add about 2.5 mL of Solution D and then add Solution D or Solution C to maintain a final composition of Solution C and Solution D in the ratio of 9:1. Sonicate briefly for complete dissolution.

Standard solution: 0.6 mg/mL of USP Doxazosin Mesylate RS in a mixture of Solution C and Solution D (9:1). Initially add about 2 mL of Solution D and then add Solution D or Solution C to maintain a final composition of Solution C and Solution D in the ratio of 9:1. Sonicate briefly for complete dissolution.

Sample solution: 0.6 mg/mL of Doxazosin Mesylate in a mixture of Solution C and Solution D (9:1). Initially add about 2 mL of Solution D and then add Solution D or Solution C to maintain a final composition of Solution C and Solution D in the ratio of 9:1. Sonicate briefly for complete dissolution,

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4-mm × 25-cm; 5-µm packing L7

Column temperature: 35°

Flow rate: 0.8 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2 between doxazosin related compound A and doxazosin related compound B, System suitability solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of doxazosin mesylate (C₂₃H₂₅N₅O₅ · CH₄O₃S) in the portion of Doxazosin Mesylate taken:

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

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

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

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

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

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

Change to read:

ORGANIC IMPURITIES

Solution A, Solution B, Solution C, Solution D, Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.0015 mg/mL, each of USP Doxazosin Mesylate RS, USP Doxazosin Related Compound A RS, USP Doxazosin Related Compound B RS. USP Doxazosin Related Compound C RS. USP Doxazosin Related Compound D RS, USP Doxazosin Related Compound E RS, USP Doxazosin Related Compound F. RS, USP Terazosin Related Compound A RS, and USP Terazosin Related Compound C RS in a mixture of Solution C and Solution D. Initially dissolve USP Doxazosin Related Compounds A, B, C, D, E, and F RS and USP Terazosin Related Compounds A and C RS in approximately 2 mL of Solution D only and then add Solution D or Solution C to maintain a final composition of Solution C and Solution D in the ratio of 9:1. Sonicate briefly for complete dissolution.

Sample solution: 0.6 mg/mL of Doxazosin Mesylate in a mixture of Solution C and Solution D (9:1). Initially add about 2 mL of Solution D and then add Solution D or Solution C to maintain a final composition of Solution C and Solution D in the ratio of 9:1. Sonicate briefly for complete dissolution.

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2 between doxazosin related compound A and doxazosin related compound B, System suitability solution

Relative standard deviation: NMT 10% for all peaks, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Doxazosin Mesylate taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of each impurity or doxazosin mesylate (for calculating unspecied impurities) from the Standard solution

C_s = concentration of the corresponding USP Reference Standard _{(ERR 1-Nov-2022)} or USP Doxazosin Mesylate RS (for calculating unspecied impurities) in the Standard solution (mg/mL)

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

M_r1 = molecular weight of the corresponding impurity in the sample (see Table 2)

M_r2 = molecular weight of corresponding impurity Reference Standard (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)piperazine, dihydrochloride.

^b This impurity exists as a mesylate salt in the sample.

^c N-1,4-Benzodioxane-2-carbonyl Piperazine.

^d 6,7-Dimethoxyquinazoline-2,4-dione.

^e 2-Chloro-4-amino-6,7-dimethoxy quinazoline.

^f 1,4-Bis(4-amino-6,7-dimethoxy-2-quinazolinyl)piperazine, dihydrochloride.

^g 1,4-Benzodioxane-2-carboxylic acid.

^h 2,4-Dichloro-6,7-dimethoxyquinazoline.

ⁱ N,N′-Bis(1,4-benzodioxane-2-carbonyl)piperazine.

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Sample: 1.0 g

Analysis: Dry the Sample under vacuum at 105° for 4 h.

Acceptance criteria: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store below 30°.

USP Reference Standards 〈11〉

USP Doxazosin Mesylate RS

USP Doxazosin Related Compound A RS

N-1,4-Benzodioxane-2-carbonyl piperazine.

C₁₃H₁₆N₂O₃               248.28

USP Doxazosin Related Compound B RS

6,7-Dimethoxyquinazoline-2,4-dione.

C₁₀H₁₀N₂O₄               222.20

USP Doxazosin Related Compound C RS

2-Chloro-4-amino-6,7-dimethoxyquinazoline.

C₁₀H₁₀ClN₃O₂            239.66

USP Doxazosin Related Compound D RS

1,4-Benzodioxane-2-carboxylic acid.

C₉H₈O₄                      180.16

USP Doxazosin Related Compound E RS

2,4-Dichloro-6,7-dimethoxyquinazoline.

C₁₀H₈Cl₂N₂O₂            259.09

USP Doxazosin Related Compound F RS

N,N′-Bis(1,4-benzodioxane-2-carbonyl)piperazine.

C₂₂H₂₂N₂O₆                410.42

USP Terazosin Related Compound A RS

1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)piperazine, dihydrochloride.

C₁₄H₁₉N₅O₂ · 2HCl    362.25

USP Terazosin Related Compound C RS

1,4-Bis(4-amino-6,7-dimethoxy-2-quinazolinyl)piperazine, dihydrochloride.

C₂₄H₂₈N₈O₄ · 2HCl    565.45