Flavoxate Hydrochloride

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₂₄H₂₅NO₄ · HCl 427.93 (USP 1-May-2021)

4H-1-Benzopyran-8-carboxylic acid, 3-methyl-4-oxo-2- phenyl-, 2-(1-piperidinyl)ethyl ester, hydrochloride;

2-Piperidinoethyl- (USP 1-May-2021) 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylate hydrochloride;

2-(Piperidin-1-yl)ethyl 3-methyl-4-oxo-2-phenyl-4H-chromene-8-carboxylate hydrochloride (USP 1-May-2021) CAS RN®: 3717-88-2; UNII: 9C05J6089W.

Change to read:

1 DEFINITION

Flavoxate Hydrochloride contains NLT 98.0% and NMT 102.0% of flavoxate hydrochloride (USP 1-May-2021) (C₂₄H₂₅NO₄ · HCl), 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.

Change to read:

C. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride

Sample solution: 10 mg/mL of Flavoxate Hydrochloride in water

Acceptance criteria: Meets the requirements (USP 1-May-2021)

3 ASSAY

Change to read:

3.1 Procedure

Solution A: Mixture of 1.0 g of sodium 1-hexanesulfonate (USP 1-May-2021) in 650 mL of water, 1 mL of triethylamine, and 1.0 mL of phosphoric acid

Mobile phase: Add 350 mL of acetonitrile to Solution A.

Standard solution: 50 μg/mL of USP Flavoxate Hydrochloride RS in Mobile phase

Sample solution: 50 μg/mL of Flavoxate Hydrochloride in Mobile phase

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 293 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: (USP 1-May-2021) 20 μL

Run time: NLT 1.5 times the retention time of flavoxate (USP 1-May-2021)

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 1.5 (USP 1-May-2021)

Relative standard deviation: NMT 0.73% (USP 1-May-2021)

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of flavoxate hydrochloride (USP 1-May-2021) (C₂₄H₂₅NO₄ · HCl) in the portion of Flavoxate Hydrochloride 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 Flavoxate Hydrochloride RS in the Standard solution

C_U = concentration of Flavoxate Hydrochloride in the Sample solution 

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Change to read:

4.1 Organic Impurities

Solution A: Transfer 0.5 mL of trifluoroacetic acid to a 1-L volumetric flask containing about 50% of the flask volume of water. Dilute with water to volume. (USP 1-May-2021)

Solution B: Acetonitrile

Solution C: Transfer 40 mL of Solution A to a 100-mL volumetric flask and dilute with water to the mark. Sonicate for about 5 min. (USP 1-May-2021)

Mobile phase: See Table 1.

Table 1

Diluent: Methanol and Solution C (50:50) (USP 1-May-2021)

Standard stock solution 1: 2 mg/mL of USP Flavoxate Hydrochloride RS in Diluent

Standard stock solution 2: 0.05 mg/mL of USP Flavoxate Related Compound A RS in Diluent

Standard stock solution 3: 0.05 mg/mL of USP Flavoxate Related Compound B RS in methanol

Standard stock solution 4: 0.05 mg/mL of USP Flavoxate Related Compound C RS prepared as follows. Dissolve USP Flavoxate Related Compound C RS first in 10% of the flask volume of methanol and then in 10% of the flask volume of Solution C. USP 1-May-2021) Dilute with Diluent to volume.

Sensitivity solution: 0.5 μg/mL of USP Flavoxate Hydrochloride RS from Standard stock solution 1 in Diluent (USP 1-May-2021)

Standard solution: 1 mg/mL of USP Flavoxate Hydrochloride RS and 5 μg/mL each of USP Flavoxate Related Compound A RS, USP Flavoxate Related Compound B RS, and USP Flavoxate Related Compound C RS in Diluent from Standard stock solutions 1, 2, 3, and 4, respectively

Sample solution: 1 mg/mL of Flavoxate Hydrochloride in Diluent

4.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Column temperature: 30°

Flow rate: 0.8 mL/min

Injection volume: (USP 1-May-2021) 10 μL

4.3 System suitability

Samples: Sensitivity solution and (USP 1-May-2021) Standard solution

[Note-See Table 2 for the relative retention times.] (USP 1-May-2021)

4.4 Suitability requirements

Resolution: NLT 2.0 between flavoxate related compound B and flavoxate related compound C, Standard solution (USP 1-May-2021)

Tailing factor: NMT 1.5 for flavoxate related compound A, flavoxate related compound B, and flavoxate related compound C, Standardsolution (USP 1-May-2021)

Relative standard deviation: NMT 2.0% for flavoxate, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-May-2021)

4.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of flavoxate related compounds A, B, and C in the portion of Flavoxate Hydrochloride taken:

Result = (r_U /r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of flavoxate from the Standard solution

C_S = concentration of USP Flavoxate Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Flavoxate Hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 2 (USP 1-May-2021) )

Calculate the percentage of any other unspecified impurity (USP 1-May-2021) in the portion of Flavoxate Hydrochloride taken:

Result = (r_U/r_T) × 100

r_U = peak response of each unspecified impurity from the Sample solution

r_T = sum of the responses of all peaks from the Sample solution

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

Table 2

5 SPECIFIC TESTS

Change to read:

Loss on Drying 〈731〉

Analysis: Dry at 105° to constant weight.

Acceptance criteria: NMT 0.5%(USP 1-May-2021)

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, protected from light; and store at room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Flavoxate Hydrochloride RS

USP Flavoxate Related Compound A RS

3-Methyl-4-oxo-2-phenyl-4H-chromene-8-carboxylic acid. (USP 1-May-2021)

C₁₇H₁₂O₄ 280.28 (USP 1-May-2021)

USP Flavoxate Related Compound B RS

Methyl 3-methyl-4-oxo-2-phenyl-4H-chromene-8-carboxylate. (USP 1-May-2021)

C₁₈H₁₄O₄ 294.31 (USP 1-May-2021)

USP Flavoxate Related Compound C RS

Ethyl 3-methyl-4-oxo-2-phenyl-4H-chromene-8-carboxylate. (USP 1-May-2021)

C₁₉H₁₆O₄ 308.33