Hydrocodone Bitartrate
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This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
C18H21NO3.C4H6O6. 2½H2O 494.49
Morphinan-6-one, 4,5-epoxy-3-methoxy-17-methyl-, (5α)-, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1), hydrate (2:5). 4,5α-Epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5) CAS RN®: 34195-34-1; 6190-38-1; UNII: NO70W886KK. Anhydrous 449.46 CAS RN®: 143-71-5; UNII: 9GU1G05Y03.
Hydrocodone Bitartrate, dried in vacuum at 105° for 2 hours, contains not less than 98.0 percent and not more than 102.0 percent of C18H21NO3.C4H6O6.
Packaging and storage—Preserve in tight, light-resistant containers.
USP Reference standards 〈11〉—
USP Dihydrocodeine Bitartrate RS
USP Hydrocodone Bitartrate RS
Identification—
Change to read:
A: Spectroscopic Identication Tests 〈197〉, Infrared Spectroscopy: 197M(CN 1-May-2020) .
Change to read:
B: Spectroscopic Identication Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U(CN 1-May-2020)
Solution: 100 µg per mL.
Medium: 0.1 N sulfuric acid.
Specific rotation 〈781S〉: between –79° and –84°.
Test solution: 20 mg, undried, per mL, in water. Calculate the result on the basis of the undried aliquot.
pH 〈791〉: between 3.2 and 3.8, in a solution (1 in 50).
Loss on drying—Dry it in vacuum at 105° for 2 hours [Note—See the Note in the Assay for precautions regarding handling of the dried material.]: it loses not less than 7.5% and not more than 12.0% of its weight.
Residue on ignition 〈281〉: not more than 0.1%.
Chloride—To 10 mL of a solution (1 in 100), acidified with nitric acid, add a few drops of silver nitrate TS: no opalescence is produced immediately.
Assay—[Note—Dry both the USP Hydrocodone Bitartrate RS and the Hydrocodone Bitartrate materials in vacuum at 105° for 2 hours. Immediately transfer the dried materials to a desiccator containing phosphorus pentoxide. Weigh each dried material individually within 1 minute, and proceed with the Assay.]
Mobile phase—Prepare a mixture of acetonitrile, water, and diethylamine (800:4:1). Prepare a filtered and degassed mixture of this solution and methanol (55:45). Make adjustments if necessary (see System Suitability under Chromatography 〈621〉). Standard preparation—Transfer about 10 mg of previously dried USP Hydrocodone Bitartrate RS, accurately weighed, to a 10-mL volumetric flask, add 5 mL of water, and mix to dissolve. Dilute with methanol to volume, and mix to obtain a solution having a known concentration of about 1 mg per mL.
Assay preparation—Transfer an accurately weighed quantity of previously dried Hydrocodone Bitartrate, equivalent to about 100 mg of hydrocodone bitartrate, C18H21NO3.C4H6O6, to a 100-mL volumetric flask, add 50 mL of water, and mix to dissolve. Dilute with methanol to volume, and mix.
Resolution solution—Prepare a solution in methanol containing about 0.4 mg of USP Dihydrocodeine Bitartrate RS and 0.6 mg of USP Hydrocodone Bitartrate RS per mL. Prepare a mixture of this solution and water (1:1).
Chromatographic system (see Chromatography 〈621〉)—The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm × 25-cm column that contains packing L3. The flow rate is about 1.5 mL per minute. Chromatograph the Resolution solution, and record the responses as directed for Procedure: the relative retention times are about 0.7 for hydrocodone and 1.0 for dihydrocodeine; and the resolution, R, between hydrocodone and dihydrocodeine is not less than 3.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 1.0%.
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 the major peaks. Calculate the quantity, in mg, of C18H21NO3.C4H6O6. in the portion of Hydrocodone Bitartrate taken by the formula:
(100C)(rU/rS)
in which C is the concentration, in mg per mL, of USP Hydrocodone Bitartrate RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
