Related compounds—
Phosphate buffer and Mobile phase—
Prepare as directed in the Assay.
Standard stock solution—
Dissolve an accurately weighed quantity of
USP Oxybutynin Chloride RS in
Mobile phase to obtain a solution having a known concentration of about 1.0 mg per mL.
System suitability solution—
Transfer 10.0 mL of the System suitability stock solution to a 100-mL volumetric flask, add 10.0 mL of the Standard stock solution, and dilute with Mobile phase to volume.
Standard solution—
Transfer 15.0 mL of the
Standard stock solution to a 100-mL volumetric flask, and dilute with
Mobile phase to volume. Transfer 5.0 mL of the solution obtained to a separate 100-mL volumetric flask, and dilute with
Mobile phase to volume. This solution contains about 7.5 µg of
USP Oxybutynin Chloride RS per mL.
Test solution—
Transfer about 50 mg of Oxybutynin Chloride, accurately weighed, to a 10-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Chromatographic system—
Prepare as directed in the Assay. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between oxybutynin related compound B and oxybutynin related compound C peaks is not less than 1.1; and the relative standard deviation for replicate injections, determined from the oxybutynin peak, is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the
Standard solution and the
Test solution into the chromatograph, record the chromatograms for a total time of not less than twice the retention time of the oxybutynin peak, and measure all the peak responses (see
Table 1 for known impurities). Calculate the percentage of each impurity in the portion of Oxybutynin Chloride taken by the formula:
(C/W)(1/F)(rU / rS),
in which
C is the concentration, in µg per mL, of
USP Oxybutynin Chloride RS in the
Standard solution; W is the weight, in mg, of Oxybutynin Chloride taken to prepare the
Test solution; F is the relative response factor for each impurity (see
Table 1 for the values); and
rU and
rS are the peak responses for each impurity obtained from the
Test solution and for the oxybutynin peak in the
Standard solution, respectively.
[NOTE—For unknown impurities, use the relative response factor of the closest known impurity.
]
Table 1
| Compound Name |
Relative
Retention
Time |
Relative
Response Factor
(F) |
Limit (%) |
Oxybutynin related
 compound A1 |
0.08 |
1.4 |
0.5 |
Diphenyl analog of
oxybutynin chloride2 |
0.37 |
2.7 |
0.1 |
Oxybutynin related
compound B3 |
0.65 |
1.3 |
1.0 |
Oxybutynin related
compound C4 |
0.79 |
1.0 |
1.0 |
Cyclohexenyl analog of
oxybutynin chloride5 |
1.8 |
0.4 |
1.0 |
Ethylpropyl analog of
oxybutynin chloride6 |
1.9 |
1.0 |
0.1 |
|
1
phenylcyclohexylglycolic acid (cyclohexylmandelic acid, or CHMA)
2
4-(diethylamino)but-2-ynyl 2-hydroxy-2,2-diphenylacetate
3
methyl ester of phenylcyclohexylglycolic acid (methyl ester of cyclohexylmandelic acid, or CHMME)
4
methylethyl analog of oxybutynin chloride (4-(ethylmethylamino) but-2-ynyl (±)-2-cyclohexyl-2-hydroxy-2-phenylacetate)
5
4-(diethylamino)but-2-ynyl (±)-2-(cyclohex-3-enyl)-2-cyclohexyl-2-hydroxyacetate
6
4-(ethylpropylamino)but-2-ynyl (±)-2-cyclohexyl-2-hydroxy-2-phenylacetate
|
In addition to not exceeding the limits for each impurity in
Table 1, not more than 0.1% of any other single impurity is found; and not more than 1.0% of total impurities is found.
Chloride content—
Dissolve about 600 mg of oxybutynin chloride, previously dried and accurately weighed, in 100 mL of water, and add 5 mL of nitric acid. Titrate (see
Titrimetry 
541
) with 0.1 N silver nitrate VS, determining the endpoint potentiometrically, using a platinum-silver chloride electrode system. Each mL of 0.1 N silver nitrate is equivalent to 3.545 mg of Cl: the content is between 8% and 10%.
Assay—
Phosphate buffer—
Dissolve about 6.67 g of monobasic potassium phosphate and 8.55 g of dibasic potassium phosphate in 1 L of water, and mix.
Mobile phase—
Prepare a filtered and degassed mixture of
Phosphate buffer and acetonitrile (51:49). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparation—
Dissolve an accurately weighed quantity of
USP Oxybutynin Chloride RS in
Mobile phase, and dilute quantitatively, and stepwise if necessary, with
Mobile phase to obtain a solution having a known concentration of about 0.1 mg per mL.
Assay preparation—
Transfer about 50 mg of Oxybutynin Chloride, accurately weighed, to a 10-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. Transfer 2.0 mL of this solution to a separate 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 210-nm detector and a 3-µm or 3.5-µm, 4.6-mm × 7.5-cm column that contains packing L7. The column temperature is maintained at 45
. The flow rate is about 1 mL per minute. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C
22H
31NO
3·HCl in the portion of Oxybutynin Chloride taken by the formula:
CD(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Oxybutynin Chloride RS in the
Standard preparation; D is the dilution factor for the
Assay preparation; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
;)
-cyclohexyl-