Add the following:
Flavoxate Hydrochloride
427.924H-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].» Flavoxate Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C24H25NO4·HCl, calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers, protected from light, and store at room temperature.
Identification—
B:
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
C:
A solution (1 in 100) meets the requirements of the silver nitrate precipitate in the test for Chloride 
191
.
191.
Loss on drying 731:
Dry at 105
to constant weight: it loses not more than 0.5% of its weight.
731:
Dry at 105 to constant weight: it loses not more than 0.5% of its weight.
Residue on ignition 281:
not more than 0.1%.
281:
not more than 0.1%.
Heavy metals, Method II 231:
0.001%.
231:
0.001%.
Related compounds—
Mobile phase—
Dissolve 1.0 g of sodium hexanesulfonate in a 500-mL volumetric flask with about 100 mL of water. Add 1.0 mL of phosphoric acid and 1.0 mL of triethylamine, and dilute with water to volume. Prepare a mixture of the resulting solution and acetonitrile (1:1). Mix well, filter and degas. Make adjustments if necessary. (see System Suitability under Chromatography 621).
621).
Standard solution—
Dissolve accurately weighed quantities of USP Flavoxate Hydrochloride RS and USP Flavoxate Related Compound A RS in Mobile phase, and dilute quantitatively and stepwise, if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.001 mg per mL of each Reference Standard.
Test solution—
Into a suitable volumetric flask dissolve an accurately weighed quantity of Flavoxate Hydrochloride in Mobile phase to obtain a solution with a nominal concentration of about 1.0 mg per mL. Mix or sonicate briefly to dissolve the sample.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 293-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 1.2 mL per minute. Chromatograph the Standard solution, and record the peak areas as directed for Procedure. Identify the peaks using the relative retention times given in Table 1. The resolution, R, between the flavoxate hydrochloride and flavoxate related compound A is not less than 6.0; the column efficiency is not less than 3000 plate counts; the tailing factor is not more than 2.0 for flavoxate related compound A; and the relative standard deviation for five replicate injections for flavoxate related compound A is not more than 2.0%.
621)—The liquid chromatograph is equipped with a 293-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 1.2 mL per minute. Chromatograph the Standard solution, and record the peak areas as directed for Procedure. Identify the peaks using the relative retention times given in Table 1. The resolution, R, between the flavoxate hydrochloride and flavoxate related compound A is not less than 6.0; the column efficiency is not less than 3000 plate counts; the tailing factor is not more than 2.0 for flavoxate related compound A; and the relative standard deviation for five replicate injections for flavoxate related compound A is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, and record the chromatograms for about 25 minutes. Measure the peak areas of all the peaks in the Test solution. Identify the peaks using the relative retention times given in Table 1.
Table 1
| Component Name | Relative Retention Time |
Relative Response Factor |
Limit (%) |
| Flavoxate hydrochloride | 1.0 | — | — |
| Flavoxate related compound A1 | 1.55 | 1.7 | 0.3 |
| Methyl ester2 | 3.45 | 1.6 | 0.1 |
| Ethyl ester3 | 4.75 | 1.4 | 0.1 |
| Any unspecified impurity | — | 1.0 | 0.1 |
| Total impurities | — | — | 1.0 |
|
1
3-Methylflavone-8-carboxylic acid.
2
3-Methylflavone-8-carboxylic acid methyl ester.
3
3-Methylflavone-8-carboxylic acid ethyl ester.
|
|||
Calculate the percentage of each impurity in the portion of Flavoxate Hydrochloride taken by the formula:
100(CS / CU)(ri / rS)(1/ F)
in which CS and CU are the concentrations of flavoxate hydrochloride, in mg per mL, of the Standard solution and the Test solution, respectively; ri is the peak response of each individual impurity; rS is the response of the flavoxate hydrochloride peak obtained from the Standard solution; and F is the relative response factor for each of the impurities relative to flavoxate hydrochloride, which is given in Table 1.
Assay—
Mobile phase—
Dissolve 1.0 g of sodium hexanesulfonate in 650 mL of water, add 1 mL of triethylamine and 1.0 mL of phosphoric acid. Filter the solution. To the resulting filtered solution add 350 mL of acetonitrile. Mix well and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Dissolve an accurately weighed quantity of USP Flavoxate Hydrochloride RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.05 mg per mL.
Assay preparation—
Dissolve an accurately weighed quantity of Flavoxate Hydrochloride in Mobile phase, and dilute quantitatively, if necessary, with Mobile phase to obtain a solution with a nominal concentration of about 0.05 mg per mL.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 293-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 3000; the tailing factor is not more than 2.0, and the relative standard deviation for five replicate injections is not more than 2.0%. [Note—The typical retention time of the flavoxate hydrochloride peak is about 4.3 minutes.]
621)—The liquid chromatograph is equipped with a 293-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 3000; the tailing factor is not more than 2.0, and the relative standard deviation for five replicate injections is not more than 2.0%. [Note—The typical retention time of the flavoxate hydrochloride peak is about 4.3 minutes.]
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the response for the flavoxate hydrochloride peak. Calculate the quantity, in percent, of C24H25NO4·HCl in the portion of Flavoxate Hydrochloride by the formula:
USP32
100(CS / CU)(rU / rS)
in which CS is the concentration of flavoxate hydrochloride, in mg per mL, in the Standard preparation; CU is the nominal concentration, in mg per mL, of Flavoxate Hydrochloride in the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.USP32
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
Chromatographic Column—
| Topic/Question | Contact | Expert Committee |
| Monograph | Ravi Ravichandran, Ph.D.
Senior Scientist 1-301-816-8330 |
(MDPP05) Monograph Development-Psychiatrics and Psychoactives |
| Reference Standards | Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org |
USP32–NF27 Page 2378
Pharmacopeial Forum: Volume No. 33(6) Page 1172
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.