Doxazosin Tablets

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

Doxazosin Tablets contain an amount of Doxazosin Mesylate equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of doxazosin (C₂₃H₂₅N₅O₅).

2 IDENTIFICATION

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

Add the following:

B. 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-2020)}

3 ASSAY

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PROCEDURE

Buffer: Transfer 3.4 g of monobasic potassium phosphate into a 1-L flask, and add 800 mL of water and 4.0 mL of triethylamine to dissolve.

Adjust with phosphoric acid to a pH of 4.5, and dilute with water to volume.

Mobile phase: Methanol and Buffer (55:45)

Diluent: Methanol and 0.1 N hydrochloric acid (90:10)

Standard solution: 0.049 mg/mL of USP Doxazosin Mesylate RS in Diluent. Sonicate to dissolve as needed. _{(USP 1-Dec-2020)}

Sample stock solution: Nominally (L/25) mg/mL of doxazosin prepared as follows, where L is the label claim in mg/Tablet. _{(USP 1-Dec-2020)} Transfer 10 Tablets, whole or ground, into a 250-mL volumetric flask, add 10 ml of water, and sonicate until the Tablets are disintegrated. Add 150 mL of Diluent, sonicate for 30 min, and dilute with Diluent to volume.

Sample solution: Nominally 0.04 mg/ml, of doxazosin in Diluent from Sample stock solution. For Tablets labeled to contain 1 mg, use the corresponding Sample stock solution directly. Centrifuge a portion of the solution and use the filtrate _{(USP 1-Dec-2020)}

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 245 nm. For Identification B, use a diode array detector in the range of 200-400 nm. _{(USP 1-Dec-2020)}

Column: 4.6-mm x 25-cm; 5-µm packing 11

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 1.6 times the retention time of doxazosin _{(USP 1-Dec-2020)}

System suitability

Sample: Standard solution

Suitability requirements

(USP 1-Dec-2020)

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxazosin (C₂₃H₂₅N₅O₅) in the portion of Tablets taken:

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

r_u = peak response of doxazosin from the Sample solution

r_s = peak response of doxazosin from the Standard solution

C_s = concentration of USP Doxazosin Mesylate RS _{(USP 1-Dec-2020)} in the Standard solution (mg/mL)

C_u = nominal concentration of doxazosin _{(USP 1-Dec-2020)} in the Sample solution (mg/mL)

M_r1 = molecular weight of doxazosin, 451.48

M_r2 = molecular weight of doxazosin mesylate, 547.58

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

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Dissolution 〈711〉

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: A known concentration of USP Doxazosin Mesylate RS in Medium.

Sample solution: Pass a portion of the solution under test through a suitable lter. Dilute with Medium as needed.

Instrumental conditions

Mode: UV

Analytical wavelength: 246 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxazosin _{(USP 1-Dec-2020)} (C₂₃H₂₅N₅O₅)_{(USP 1-Dec-2020)} dissolved:

Result = (A_u /A_s ) × C_s × V × (M_r1 /M_r2 ) × (1/L) × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

M_r1 = molecular weight of doxazosin, 451.48

M_r2 = molecular weight of doxazosin mesylate, 547.58

L = label claim of doxazosin (mg/Tablet) _{(USP 1-Dec-2020)}

Tolerances: NLT 70% (Q) of the labeled amount of doxazosin _{(USP 1-Dec-2020)} (C H N O ) _{(USP 1-Dec-2020)} is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

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ORGANIC IMPURITIES: Protect the solutions containing doxazosin from light.

Buffer: 3.4 g/L of monobasic potassium phosphate, prepared by dissolving 3.4 g of monobasic potassium phosphate in 1 L of water

Solution A: Mix 90 mL of acetonitrile with 920 mL of Buffer. Add 1 mL of triethylamine and adjust with phosphoric acid to a pH of 3.0.

Solution B: Mix 500 mL of acetonitrile with 500 mL of Buffer. Add 1 mL of triethylamine and adjust with phosphoric acid to a pH of 3.0.

Mobile phase: See Table 1.

Table 1

Diluent: Methanol, phosphoric acid, and water (500:1:500)

System suitability solution: 2 µg/mL each of USP Doxazosin Related Compound A RS and USP Doxazosin Related Compound G RS in Diluent

Standard stock solution A: 24 µg/mL of USP Doxazosin Mesylate RS in Diluent. Sonicate to dissolve as needed.

Standard stock solution B: 25 µg/mL of USP Terazosin Related Compound A RS (equivalent to 20 µg/ml. of terazosin related compound A free base) in Diluent. Sonicate to dissolve as needed.

Sensitivity solution: 0.6 µg/mL of USP Doxazosin Mesylate RS in Diluent from Standard stock solution A

Standard solution: 2.4 µg/mL of USP Doxazosin Mesylate RS and 6.25 µg/mL of USP Terazosin Related Compound A.RS (equivalent to 5 µg/mL of terazosin related compound A free base) in Diluent from Standard stock solution A and Standard stock solution B. Sonicate to dissolve and pass through a PVDF filter or other suitable filter of 0.45-µm pore size as needed.

Sample solution: Nominally 1 mg/mL of doxazosin prepared as follows. Transfer a nominal amount of 5 mg of doxazosin from NLT 20 finely powdered Tablets to a suitable tube. Add 5 mL of Diluent. Vortex and sonicate for 15 min.

[NOTE-If needed, centrifuge the solution and pass the supernatant through a PVDF filter or other suitable filter of 0.45-µm pore size. Discard NLT 3 mL of the filtrate.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 25-cm; 5-µm packing L10

Flow rate: 1 mL/min

Injection volume: 30 µL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[NOTE-See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 1 between the doxazosin related compound G and doxazosin related compound A peaks, System suitability solution

Tailing factor: NMT 1.5 for the doxazosin peak, Standard solution

Relative standard deviation: NMT 5.0% for the doxazosin and terazosin related compound A peaks, Standard solution

Signal-to-noise ratio: NLT 10 for the doxazosin peak, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of terazosin related compound A free base in the portion of Tablets taken:

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

r_u = peak response of terazosin related compound A from the Sample solution

r_s = peak response of terazosin related compound A from the Standard solution

C_s = concentration of USP Terazosin Related Compound A RS in the Standard solution (µg/mL)

C_u = nominal concentration of doxazosin in the Sample solution (µg/mL)

M_r1 = molecular weight of terazosin related compound A free base, 289.34

M_r2 = molecular weight of terazosin related compound A, 362.25

Calculate the percentage of any other specied and unspecied impurities in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × (M_r1 /M_r2 ) × 100

r_u = peak response of each corresponding impurity from the Sample solution

r_s = peak response of doxazosin from the Standard solution

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

C_u = nominal concentration of doxazosin in the Sample solution (µg/mL)

F = relative response factor (see Table 2)

M_r1 = molecular weight of doxazosin free base, 451.48

M_r2 = molecular weight of doxazosin mesylate, 547.58

Acceptance criteria: See Table 2.

Table 2

^a 6,7-Dimethoxy-2-(piperazin-1-yl)quinazolin-4-amine.

^b 4-Amino-6,7-dimethoxyquinazolin-2(1H)-one.

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

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

^e N,N'-Bis(1,4-benzodioxane-2-carbonyl)piperazine.

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in tight containers. Store at controlled room temperature. _{(USP 1-Dec-2020)}

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USP Reference Standards 〈11〉

USP Doxazosin Mesylate RS

USP Doxazosin Related Compound A RS

N-1,4-Benzodioxane-2-carbonyl Piperazine hydrochloride.

C₁₃H₁₆N₂O₃ · HCl           284.74

USP Doxazosin Related Compound G RS

4-Amino-6,7-dimethoxyquinazolin-2(1H)-one hydrochloride.

C₁₀H₁₁N₃O₃ · HCl           257.67

USP Terazosin Related Compound A RS

6,7-Dimethoxy-2-(piperazin-1-yl)quinazolin-4-amine dihydrochloride.

C₁₄H₁₉N₅O₂ · 2HCl        362.25 _{(USP 1-Dec-2020)}