Flavoxate Hydrochloride
(flay vox' ate hye'' droe klor' ide).
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C24H25NO4·HCl 427.92
4H-1-Benzopyran-8-carboxylic acid, 3-methyl-4-oxo-2-phenyl-, 2-(1-piperidinyl)ethyl ester, hydrochloride;    
2-Piperidinoethyl 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylate hydrochloride     [3717-88-2].
DEFINITION
Flavoxate Hydrochloride contains NLT 98.0% and NMT 102.0% of C24H25NO4·HCl, calculated on the dried basis.
IDENTIFICATION
•  B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
•  C. Identification Tests—General, Chloride 191: A solution of 10 mg/mL meets the requirements of the silver nitrate precipitate.
ASSAY
•  Procedure
Solution A:  Mixture of 1.0 g of sodium hexanesulfonate 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
Chromatographic system 
Mode:  LC
Detector:  UV 293 nm
Column:  4.6-mm × 15-cm; 5-µm packing L1
Flow rate:  1 mL/min
Injection size:  20 µL
System suitability 
Sample:  Standard solution
[Note—The retention time of flavoxate is about 4.3 min. ]
Suitability requirements 
Column efficiency:  NLT 3000 theoretical plates
Tailing factor:  NMT 2.0
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C24H25NO4·HCl in the portion of Flavoxate Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS == peak response from the Standard solution
CS== concentration of USP Flavoxate Hydrochloride RS in the Standard solution (mg/mL)
CU== nominal concentration of Flavoxate Hydrochloride in the Sample solution (mg/mL)
Acceptance criteria:  98.0%–102.0% on the dried basis
IMPURITIES
Inorganic Impurities 
•  Residue on Ignition 281: NMT 0.1%
•  Heavy Metals, Method II 231: NMT 10 ppm
Organic Impurities 
•  Procedure
Solution A:  0.05% (v/v) trifluoroacetic acid in water
Solution B:  Acetonitrile
Mobile phase:  See the gradient table below.
Time
(min)
Solution A
(%)
Solution B
(%)
0 68 32
15 68 32
25 20 80
35 20 80
36 68 32
41 68 32
Diluent:  Methanol and 0.02% trifluoroacetic acid (1:1)
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 methanol using 10% of final volume, then fill 10% of final volume with 0.02% trifluoroacetic acid. Dilute with Diluent to volume.
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
Chromatographic system 
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 size:  10 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Resolution:  NLT 2.0 between the flavoxate related compound B and flavoxate related compound C peaks
Tailing factor:  NMT 1.5 for the flavoxate related compounds A, B, and C peaks
Relative standard deviation:  NMT 2.0% for the flavoxate peak
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 = (rU/rS) × (CS/CU) × (1/F) × 100
rU== peak response of each individual impurity from the Sample solution
rS== peak response of flavoxate from the Standard solution
CS== concentration of USP Flavoxate Hydrochloride RS in the Standard solution (mg/mL)
CU== concentration of Flavoxate Hydrochloride in the Sample solution (mg/mL)
F== relative response factor (see Impurity Table 1)
Calculate the percentage of any other unspecified degradation product in the portion of Flavoxate Hydrochloride taken:
Result = (rU/rT) × 100
rU== peak response of each unspecified impurity from the Sample solution
rT== sum of responses of all peaks from the Sample solution
Acceptance criteria 
Individual impurities:  See Impurity Table 1.
Total impurities:  1.0%
Impurity Table 1
Name Relative
Retention
Time
Relative
Response
Factor
Acceptance
Criteria,
NMT (%)
Flavoxate 1.0
Flavoxate related compound Aa,* 2.8 1.6 0.3
Flavoxate related compound Bb,* 3.5 1.5 0.1
Flavoxate related compound Cc,* 3.7 1.4 0.1
Any single unspecified degradation product 1.0 0.1
a  3-Methylflavone-8-carboxylic acid.
b  3-Methylflavone-8-carboxylic acid methyl ester.
c  3-Methylflavone-8-carboxylic acid ethyl ester.
*  For identification and system suitability purposes only.
SPECIFIC TESTS
•  Loss on Drying 731: Dry a sample at 105 to constant weight: it loses NMT 0.5% of its weight.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed containers, protected from light; and store at room temperature.
•  USP Reference Standards 11
USP Flavoxate Hydrochloride RS
USP Flavoxate Related Compound A RS
3-Methylflavone-8-carboxylic acid.
    C17H12O4         280.27
USP Flavoxate Related Compound B RS
3-Methylflavone-8-carboxylic acid methyl ester.
    C18H14O4        294.30
USP Flavoxate Related Compound C RS
3-Methylflavone-8-carboxylic acid ethyl ester.
    C19H16O4        308.33
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Ravi Ravichandran, Ph.D.
Principal Scientific Liaison
1-301-816-8330
(SM42010) Monographs - Small Molecules 4
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 3198
Pharmacopeial Forum: Volume No. 35(6) Page 1454