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.
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.
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.
Related compounds—
[NOTE—For the test for
Related compounds and in the
Assay, dry both
USP Hydrocodone Bitartrate RS and
USP Dihydrocodeine Bitartrate RS under vacuum at 105
for 2 hours. Immediately transfer the dried materials to a desiccator containing phosphorus pentoxide. Immediately weigh each dried material.
]
Solution A, Solution B, Mobile phase, and Chromatographic system—
Proceed as directed in the Assay.
Test solution—
Use the Assay preparation.
System suitability solution—
Combine about 1.5 mg of
USP Dihydrocodeine Bitartrate RS and 1.0 mL of the
Standard preparation prepared for the
Assay in a 200-mL volumetric flask. Dilute with
Solution A to volume, and mix.
Chromatographic system (see Chromatography 621)—
Proceed as directed in the
Assay. Chromatograph the
System suitability solution, and record the peak responses as directed for
Procedure: the relative retention times are about 0.89 for dihydrocodeine and 1.0 for hydrocodone; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Inject equal volumes (about 20 µL) of the
Test solution and the
System suitability solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of dihydrocodeine bitartrate and any unknown impurities in the portion of Hydrocodone Bitartrate taken by the formula:
10,000(C/W)F(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Hydrocodone Bitartrate RS in the
System suitability solution; W is the quantity, in mg, of Hydrocodone Bitartrate taken to prepare the
Test solution; F is the relative response factor and is equal to the values given in the following table;
rU is the individual peak response of each impurity in the test solution; and
rS is the response of hydrocodone bitartrate in the
System suitability solution: not more than 0.5% of any individual impurity is found, and not more than 2.0% of total impurities is found.
Hydrocodone Bitartrate
and
Related Compounds |
Relative
Retention Time |
Relative
Response
Factor |
| Dihydrocodeine bitartrate |
0.89 |
0.81 |
Hydrocodone diol
bitartrate |
0.92 |
0.76 |
| Hydrocodone bitartrate |
1.00 |
1.00 |
Dihydrothebainone
bitartrate |
1.03 |
— |
Hydrocodone aldol dimer
bitartrate |
1.10 |
0.96 |
7-Cyclohexenyl hydroco-
done bitartrate |
1.50 |
1.00 |
| Benzophenone |
1.79 |
— |
| Other impurities |
— |
1.0 |
Assay—
[NOTE—See the
Note in the test for
Related compounds before performing the
Assay.]
Solution A—
Dissolve 5.75 g of monobasic ammonium phosphate in about 900 mL of water in a 1000-mL volumetric flask, adjust with phosphoric acid to a pH of 3.0 ± 0.1, dilute with methanol to volume, and mix.
Solution B—
Prepare a filtered and degassed mixture of methanol and water (80:20).
Mobile phase—
Use variable mixtures of
Solution A and
Solution B as directed for
Chromatographic system. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparation—
Dissolve an accurately weighed quantity of
USP Hydrocodone Bitartrate RS in
Solution A to obtain a solution having a known concentration of about 1.5 mg per mL.
Assay preparation—
Transfer an accurately weighed quantity of previously dried Hydrocodone Bitartrate, equivalent to about 150 mg of hydrocodone bitartrate, to a 100-mL volumetric flask, dissolve in and dilute with Solution A to volume, and mix.
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 5-µm packing L7. The column temperature is maintained at 60
. The flow rate is about 1.2 mL per minute. The chromatograph is programmed as follows.
Time
(minutes) |
Solution A
(%) |
Solution B
(%) |
Elution |
| 0 |
100 |
0 |
equilibrium |
| 0–6 |
100 |
0 |
isocratic |
| 6–30 |
100®0 |
0®100 |
linear gradient |
| 30–31 |
0®100 |
100®0 |
linear gradient |
Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the tailing factor is not more than 1.0; 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 peak responses. Calculate the quantity, in mg, of hydrocodone bitartrate (C
18H
21NO
3·C
4H
6O
6) 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.
;)
)-, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1), hydrate (2:5).