Oxybutynin Chloride
(ox'' i bue' ti nin klor' ide).
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393.95Benzeneacetic acid,
-cyclohexyl--hydroxy-, 4-(diethylamino)-2-butynyl ester hydrochloride, (±)-.
4-(Diethylamino)-2-butynyl (±)-
-phenylcyclohexaneglycolate hydrochloride
[1508-65-2].» Oxybutynin Chloride contains not less than 97.0 percent and not more than 102.0 percent of C22H31NO3·HCl, calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
USP Reference standards 
11
—
11—
USP Oxybutynin Chloride RS 
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USP Oxybutynin Related Compound B RS
Methyl ester of phenylcyclohexylglycolic acid, or CHMME (cyclohexyl mandelic acid methyl ester).
Methyl ester of phenylcyclohexylglycolic acid, or CHMME (cyclohexyl mandelic acid methyl ester).
USP Oxybutynin Related Compound C RS
Methylethyl analog of oxybutynin chloride, or (4-(ethylmethylamino) but-2-ynyl (±) 2-cyclohexyl-2-hydroxy-2-phenylacetate hydrochloride).
Methylethyl analog of oxybutynin chloride, or (4-(ethylmethylamino) but-2-ynyl (±) 2-cyclohexyl-2-hydroxy-2-phenylacetate hydrochloride).
Identification,
Infrared Absorption 197K.
197K.
Melting range 741:
between 124
and 129.
741:
between 124 and 129.
Loss on drying 731:
Dry it at 105 for 2 hours: it loses not more than 3% of its weight.
731:
Dry it at 105 for 2 hours: it loses not more than 3% of its weight.
Residue on ignition 281:
not more than 0.1%.
281:
not more than 0.1%.
Heavy metals, Method I 231:
0.002%.
231:
0.002%.
Related compounds—
Phosphate buffer and Mobile phase—
Prepare as directed in the Assay.
System suitability stock solution—
Dissolve accurately weighed quantities of USP Oxybutynin Related Compound B RS and USP Oxybutynin Related Compound C RS in Mobile phase to obtain a solution having known concentrations of about 100 µg of each USP Reference Standard per mL.
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 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:
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.
(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 1.0. ]
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
|
|||
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%.
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).
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%.
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 C22H31NO3·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.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Elena Gonikberg, Ph.D.
Principal Scientific Liaison 1-301-816-8251 |
(SM32010) Monographs - Small Molecules 3 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4164
Pharmacopeial Forum: Volume No. 33(5) Page 932