Oxycodone Terephthalate
(ox'' i koe' done ter'' e thal' ate).
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796.86Morphinan-6-one, 4,5-epoxy-14-hydroxy-3-methoxy-17-methyl-, 1,4-benzenedicarboxylate (2:1 salt), (5
).
4,5
-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one 1,4-benzenedicarboxylate (2:1 salt)
[64336-55-6].» Oxycodone Terephthalate contains not less than 97.0 percent and not more than 103.0 percent of (C18H21NO4)2·C8H6O4, calculated on the dried basis.
Packaging and storage—
Preserve in tight containers.
USP Reference standards 
11
—
11—
USP Oxycodone RS 
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Identification—
A:
Transfer 50 mL of the filtrate retained from the test for Terephthalate acid content to a 125-mL conical flask. Render the solution alkaline with 6 N ammonium hydroxide. Allow the mixture to stand until a precipitate is formed. Filter, wash the precipitate with 50 mL of cold water, and dry for 2 hours at 105
: the precipitate so obtained melts between 218 and 223, but the range between beginning and end of melting does not exceed 2 (see Melting Range or Temperature 741).
: the precipitate so obtained melts between 218 and 223, but the range between beginning and end of melting does not exceed 2 (see Melting Range or Temperature 741).
B:
Infrared Absorption 197K: using a portion of the dried precipitate obtained in Identification test A, and the USP Oxycodone RS.
197K: using a portion of the dried precipitate obtained in Identification test A, and the USP Oxycodone RS.
C: Ultraviolet Absorption 197U—
197U—
Solution:
150 µg per mL.
Medium:
0.1 N hydrochloric acid.
Exhibits a maximum at 280 nm.
Loss on drying 731—
Dry it at 105 for 4 hours: it loses not more than 1.5% of its weight.
731—
Dry it at 105 for 4 hours: it loses not more than 1.5% of its weight.
Residue on ignition 281:
not more than 1%.
281:
not more than 1%.
Related compounds—
Solution A—
Dissolve 2.2 g of sodium 1-octanesulfonate in 850 mL of water, and add 150 mL of methanol, 20 mL of glacial acetic acid, and 1.0 mL of triethylamine. Mix, pass through a filter having a 0.5-µm or finer porosity, and degas.
Solution B—
Dissolve 2.2 g of sodium 1-octanesulfonate in 500 mL of water, and add 500 mL of methanol, 20 mL of glacial acetic acid, and 1.0 mL of triethylamine. Mix, pass through a filter having a 0.5-µm or finer porosity, and degas.
Mobile phase—
Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments to either Solution as necessary (see System Suitability under Chromatography 621).
621).
Diluting solution—
Use 0.1 N hydrochloric acid.
Standard preparation—
Quantitatively dissolve an accurately weighed quantity of USP Oxycodone RS in Diluting solution to obtain a stock standard solution having a known concentration of about 0.9 mg per mL. Transfer 10.0 mL of this stock standard solution to a 100-mL volumetric flask, add 20 mL of methanol, dilute with Diluting solution to volume, and mix.
Resolution solution—
Dissolve a quantity of 4-hydroxybenzoic acid isopropyl ester in methanol to obtain a solution having a concentration of about 0.05 mg per mL. Transfer 20 mL of this solution and 10 mL of the stock standard solution used to prepare the Standard preparation to a 100-mL volumetric flask, dilute with Diluting solution to volume, and mix.
Test preparation—
Transfer about 110 mg of Oxycodone Terephthalate, accurately weighed, to a 10-mL volumetric flask, add 8 mL of methanol, and shake by mechanical means for about 20 minutes to dissolve. Dilute with methanol to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 15-cm column that contains packing L1, is maintained at 45 ± 1, and is programmed to provide variable mixtures of Mobile phase. The flow rate is about 1.5 mL per minute. Equilibrate the system with a mobile phase consisting of a mixture of 90% Solution A and 10% Solution B. After each injection of the Standard preparation, Resolution solution, and Test preparation, the composition of the mobile phase is changed linearly over the next 30 minutes so that at the end of that time it consists of 80% Solution A and 20% Solution B, and is then changed linearly over the next 20 minutes so that at the end of that time it consists of 100% Solution B, which is then maintained for 5 minutes. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between the oxycodone peak and the 4-hydroxybenzoic acid isopropyl ester peak is not less than 8. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5.0%.
621)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 15-cm column that contains packing L1, is maintained at 45 ± 1, and is programmed to provide variable mixtures of Mobile phase. The flow rate is about 1.5 mL per minute. Equilibrate the system with a mobile phase consisting of a mixture of 90% Solution A and 10% Solution B. After each injection of the Standard preparation, Resolution solution, and Test preparation, the composition of the mobile phase is changed linearly over the next 30 minutes so that at the end of that time it consists of 80% Solution A and 20% Solution B, and is then changed linearly over the next 20 minutes so that at the end of that time it consists of 100% Solution B, which is then maintained for 5 minutes. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between the oxycodone peak and the 4-hydroxybenzoic acid isopropyl ester peak is not less than 8. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5.0%.
Procedure—
Inject about 25 µL of the Standard preparation and the Test preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in relation to the oxycodone component taken by the formula:
1000(398.43/315.37)(C/M)(ri / rS)
in which 398.43 is one-half of the molecular weight of oxycodone terephthalate; 315.37 is the molecular weight of oxycodone; C is the concentration, in mg per mL, of USP Oxycodone RS in the Standard preparation; M is the quantity, in mg, of Oxycodone Terephthalate taken to prepare the Test preparation; ri is the area of an individual impurity peak obtained from the Test preparation; and rS is the area of the oxycodone peak obtained from the Standard preparation. If any impurity is found having a retention time of about 2 in relation to that of the oxycodone peak, divide its apparent percentage by 4.8: no individual impurity exceeds 1.0%, and the sum of all impurities does not exceed 2.0%.
Terephthalic acid content—
Transfer about 1 g, accurately weighed, to a 50-mL beaker. Add 25 mL of 0.2 N hydrochloric acid, and heat to boiling with continuous stirring. Cover the beaker with a watch glass, and allow to cool to room temperature. Pass the suspension through a tared, medium-porosity filtering crucible. Transfer any material remaining in the beaker to the crucible with the aid of small portions of cold 0.2 N hydrochloric acid. Wash the material in the crucible with several portions of cold 0.2 N hydrochloric acid. [note—Reserve the combined filtrates for use in Identification test A. ] Dry the material in the crucible at 105 for 1 hour, allow to cool, and reweigh. The material in the crucible is terephthalic acid. Determine the weight of terephthalic acid, and calculate the percentage of terephthalic acid: between 20.2% and 21.5% of C8H6O4 in the Oxycodone Terephthalate, calculated on the dried basis, is found.
for 1 hour, allow to cool, and reweigh. The material in the crucible is terephthalic acid. Determine the weight of terephthalic acid, and calculate the percentage of terephthalic acid: between 20.2% and 21.5% of C8H6O4 in the Oxycodone Terephthalate, calculated on the dried basis, is found.
Assay—
Mobile phase—
Dissolve 2.2 g of sodium 1-octanesulfonate in 740 mL of water, add 260 mL of methanol, 10 mL of glacial acetic acid, and 0.1 mL of triethylamine. Mix, and adjust with 5 N sodium hydroxide to a pH of 6.5 ± 0.1. Pass through a suitable filter having a 0.5-µm or finer porosity, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Diluting solution—
Use 0.1 N hydrochloric acid.
Internal standard solution—
Transfer about 50 mg of ethylparaben to a 500-mL volumetric flask, add 10 mL of methanol, and swirl to dissolve. Dilute with Diluting solution to volume, and mix.
Standard preparation—
Dissolve an accurately weighed quantity of USP Oxycodone RS in Diluting solution, and quantitatively dilute with Diluting solution to obtain a stock solution having a known concentration of about 0.75 mg per mL. Transfer 15.0 mL of this stock solution to a 100-mL volumetric flask, add 20.0 mL of Internal standard solution, dilute with Diluting solution to volume, and mix to obtain a Standard preparation having a known concentration of about 0.1125 mg of USP Oxycodone RS per mL.
Assay preparation—
Transfer about 142 mg of Oxycodone Terephthalate, accurately weighed, to a 200-mL volumetric flask, dilute with Diluting solution to volume, and mix. Filter this solution, discarding the first 5 mL of the filtrate. Transfer 10.0 mL of the clear filtrate to a 50-mL volumetric flask, add 10.0 mL of Internal standard solution, dilute with Diluting solution to volume, and mix. Use this solution as the Assay preparation.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 15-cm column that contains packing L1 and is maintained at a temperature of 50 ± 1.0. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the responses as directed for Procedure: the column efficiency, determined from the oxycodone peak, is not less than 1800 theoretical plates; the resolution, R, between oxycodone and ethylparaben is not less than 6; and the relative standard deviation for replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 15-cm column that contains packing L1 and is maintained at a temperature of 50 ± 1.0. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the responses as directed for Procedure: the column efficiency, determined from the oxycodone peak, is not less than 1800 theoretical plates; the resolution, R, between oxycodone and ethylparaben is not less than 6; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 30 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms for a period of time that is twice the retention time of the main oxycodone peak, and measure the peak responses for ethylparaben and oxycodone. Calculate the quantity, in mg, of (C18H21NO4)2·C8H6O4 in the portion of Oxycodone Terephthalate taken by the formula:
(398.43/315.37)(1000C)(RU / RS)
in which 398.43 is one-half of the molecular weight of oxycodone terephthalate; 315.37 is the molecular weight of oxycodone; C is the concentration, in mg per mL, of USP Oxycodone RS in the Standard preparation; and RU and RS are the ratios of the peak response of oxycodone to that of ethylparaben 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 | Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison 1-301-816-8139 |
(SM22010) Monographs - Small Molecules 2 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4178
Pharmacopeial Forum: Volume No. 29(3) Page 645