» Naltrexone Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C20H23NO4·HCl, calculated on the anhydrous, solvent-free basis.
Packaging and storage Preserve in tight containers.
Completeness of solution 641 A 650-mg portion dissolves in 10 mL of water to yield a clear solution.
Identification, Infrared Absorption 197K
Test specimen Dissolve about 150 mg in 25 mL of water in a small separator, add a few drops of 6 N ammonium hydroxide slowly until no more white precipitate is formed. Extract with three 5-mL portions of chloroform, filter the extracts through a dry filter, collecting the filtrate in a small flask. Evaporate the filtrate on a steam bath to dryness, and dry the residue at 105 for one hour.
Specific rotation 781S: between 187 and 197, calculated on the anhydrous, solvent-free basis.
Test solution: 25 mg per mL, in water.
Water, Method I 921 Determine the water content as directed. [noteThe result of this test is used in the calculation of Limit of total solvents.]
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: not more than 0.002%.
Limit of total solvents
Internal standard stock solution Transfer 6.0 mL of isopropyl alcohol to a 500-mL volumetric flask, dilute with water to volume, and mix. [noteThe isopropyl alcohol must be free of alcohol impurities.]
Internal standard solution Transfer 5.0 mL of the Internal standard stock solution to a 100-mL volumetric flask, dilute with water to volume, and mix.
Standard solution Prepare a solution of methanol and alcohol (C2H5OH) in water to obtain a solution having a known concentration of about 16 mg of each per mL. Transfer 3.0 mL of this solution and 5.0 mL of Internal standard stock solution to a 100-mL volumetric flask, dilute with water to volume, and mix.
Test solution Transfer about 75 mg of Naltrexone Hydrochloride, accurately weighed, to a suitable container, add 5.0 mL of Internal standard solution, and shake to dissolve.
Chromatographic system (see Chromatography 621) The gas chromatograph is equipped with a flame-ionization detector and a 4-mm × 1.8-m glass column packed with 80- to 100-mesh support S3. The column temperature is maintained at 150, and the injection port and detector temperatures are maintained at 170. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.24 for methanol, 0.53 for alcohol, and 1.0 for isopropyl alcohol.
Procedure Separately inject equal volumes (about 5 µL) of the Standard solution and the Test solution into the gas chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentages of methanol and alcohol in the portion of Naltrexone Hydrochloride taken by the formula:
100(CS / CU)(RU / RS)in which CS is the concentration, in mg per mL, of methanol or alcohol (C2H5OH) in the Standard solution; CU is the concentration, in mg per mL, of Naltrexone Hydrochloride in the Test solution; and RU and RS are the peak response ratios of methanol or alcohol to isopropyl alcohol obtained from the Test solution and the Standard solution, respectively. To the sum of the percentages of methanol and alcohol, add the percentage of water as determined in the test for Water: the sum of water and alcoholic solvents is not more than 5.0% for the anhydrous form, and not more than 11.0% for the dihydrate form.
Related compounds Proceed as directed in the Assay. From the chromatogram of the Assay preparation, calculate the percentage of each related compound in Naltrexone Hydrochloride taken by the formula:
10F(C/W)(rU / rS)in which F is the relative response factor for each impurity; C is the concentration, in mg per mL, of USP Naltrexone RS in the Standard preparation; W is the weight, in mg, of Naltrexone Hydrochloride taken for the Assay preparation; rU is the peak response of the relevant related compound obtained from the Assay preparation; and rS is the peak response of naltrexone obtained from the Standard preparation. [noteThe relative response factor is 0.3 for 2,2¢-bisnaltrexone and 10-ketonaltrexone, and 1.0 for all other related compound peaks.] Not more than 0.5% of any individual related compound is found; and the total of all related compounds is not more than 1.5%.
Content of chloride Transfer about 300 mg, accurately weighed, to a 250-mL conical flask, add 50 mL of methanol, 50 mL of water, and 3 mL of nitric acid, and mix to dissolve. Titrate with 0.1 N silver nitrate VS, determining the endpoint potentiometrically. Each mL of 0.1 N silver nitrate is equivalent to 3.545 mg of chloride: between 9.20% and 9.58%, calculated on the anhydrous, solvent-free basis is found.
Solution A Dissolve about 1.08 g of sodium 1-octanesulfonate and about 23.8 g of sodium acetate in 800 mL of water. Add 1.0 mL of triethylamine and 200 mL of methanol, and mix. Adjust with glacial acetic acid to a pH of 6.5 ± 0.1. Filter and degas prior to use.
Solution B Dissolve about 1.08 g sodium 1-octanesulfonate and about 23.8 g sodium acetate in 400 mL of water. Add 1.0 mL triethylamine and 600 mL of methanol, and mix. Adjust with glacial acetic acid to a pH of 6.5 ± 0.1. Filter and degas prior to use.
Mobile phase Use variable mixtures of Solution A and Solution B as directed for Chromatographic system.
Standard preparation Transfer an accurately weighed quantity of about 22.5 mg of USP Naltrexone RS to a 10-mL volumetric flask. Add 1.5 mL of methanol and 0.6 mL of 0.1 N hydrochloric acid. Dissolve by swirling the flask, and dilute with 0.1 M phosphoric acid to volume.
Resolution solution Transfer about 3.0 mg, accurately weighed, of USP Naltrexone Related Compound A RS to a 10-mL volumetric flask. Add 3.0 mL of methanol, and dissolve by swirling. Dilute with 0.1 M phosphoric acid to volume, and mix. Transfer 0.5 mL of this solution to a 10-mL volumetric flask, add 5.0 mL of Standard preparation, dilute with 0.1 M phosphoric acid to volume, and mix.
Assay preparation Transfer an accurately weighed quantity of about 25 mg of Naltrexone Hydrochloride to a 10-mL volumetric flask. Dissolve in and dilute with 0.1 M phosphoric acid 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 and is programmed to provide, at a flow rate of about 1 mL per minute, a variable mixture of Solution A and Solution B. At the time the specimen is injected into the chromatograph, the percentage of Solution A is 100%; over the next 35 minutes, the proportion of Solution B is increased linearly to 100%, and then over the next minute, decreased linearly to 100% of Solution A. Allow the system to equilibrate until the late eluting peak has been observed, approximately 17 minutes later. Chromatograph about 20 µL of the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.55 for noroxymorphone, 0.70 for 10-hydroxynaltrexone, 1.0 for naltrexone, 1.26 for naltrexone related compound A, 1.80 for 2,2¢-bisnaltrexone, and 1.99 for 10-ketonaltrexone; the resolution, R, between naltrexone and naltrexone related compound A is not less than 2.0; the tailing factor for the naltrexone peak is not greater than 1.4; and the relative standard deviation for replicate injections is not more than 2.0%.
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 responses for all the peaks. Calculate the quantity, in mg, of C20H23NO4·HCl in the portion of Naltrexone Hydrochloride taken by the formula:
(377.86/341.41)10C(rU / rS)in which 377.86 and 341.41 are the molecular weights of naltrexone hydrochloride and naltrexone, respectively; C is the concentration, in mg per mL, of USP Naltrexone RS in the Standard preparation; and rU and rS are the peak responses of naltrexone obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information Please check for your question in the FAQs before contacting USP.Chromatographic Column
USP32NF27 Page 3028Pharmacopeial Forum: Volume No. 34(2) Page 283
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.