United States Pharmacopeia online
Select Pharmacopoeia
Minocycline Hydrochloride
Click to View Image
C23H27N3O7·HCl 493.95
2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11dioxo-, monohydrochloride, [4S-(4,4a,5a,12a)]-.
4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride [13614-98-7].
» Minocycline Hydrochloride contains the equivalent of not less than 890 µg and not more than 950 µg of minocycline (C23H27N3O7) per mg, calculated on the anhydrous basis.
Packaging and storage— Preserve in tight containers, protected from light.
Labeling— Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
Identification, Infrared Absorption 197K: previously dried at 100 for 2 hours.
Crystallinity 695: meets the requirements.
pH 791: between 3.5 and 4.5, in a solution containing the equivalent of 10 mg of minocycline per mL.
Water, Method I 921: between 4.3% and 8.0%.
Residue on ignition 281: not more than 0.15%.
Chromatographic purity—
Mobile phase, Resolution solution, and Chromatographic system— Proceed as directed in the Assay.
Test solution 1— Transfer about 25 mg of Minocycline Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dilute with water to volume, and mix. Protect this solution from light, store in a refrigerator, and use within 3 hours.
Test solution 2— Transfer 1.0 mL of Test solution 1 to a 50-mL volumetric flask, dilute with water to volume, and mix. Protect this solution from light, store in a refrigerator, and use within 3 hours.
Test solution 3— Transfer 6.0 mL of Test solution 2 to a 10-mL volumetric flask, dilute with water to volume, and mix. Protect this solution from light, store in a refrigerator, and use within 3 hours.
Procedure— Separately inject equal volumes (about 20 µL) of Test solution 1, Test solution 2, and Test solution 3 into the chromatograph, record the chromatograms, and measure the areas for all the peaks. [NOTE—Record the chromatogram of Test solution 1 for a period of time that is about 2.6 times the retention time of minocycline.] Calculate the percentage of epiminocycline in the portion of Minocycline Hydrochloride taken by the formula:
1.2rE1/rM3,
in which rE1 is the peak response for epiminocycline obtained from Test solution 1; and rM3 is the peak response for minocycline obtained from Test solution 3. Not more than 1.2% is found. Calculate the total percentage of impurities other than epiminocycline in the portion of Minocycline Hydrochloride taken by the formula:
2rs / rM2,
in which rs is the sum of the responses of all impurity peaks other than epiminocycline obtained from Test solution 1; and rM2 is the peak response for minocycline obtained from Test solution 2. Not more than 2.0% of other impurities is found.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Other requirements— Where the label states that Minocycline Hydrochloride is sterile, it meets the requirements for Sterility Tests 71 and for Bacterial endotoxins under Minocycline for Injection. Where the label states that Minocycline Hydrochloride must be subjected to further processing during the preparation of injectable dosage forms, it meets the requirements for Bacterial endotoxins under Minocycline for Injection.
Assay—
Mobile phase— Prepare a mixture of 0.2 M ammonium oxalate, 0.01 M edetate disodium, dimethylformamide, and tetrahydrofuran (600:180:120:80). Adjust with ammonium hydroxide to a pH of 7.2, and pass through a filter having a 0.5-µm or finer porosity. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Minocycline Hydrochloride RS in water to obtain a solution having a known concentration of about 500 µg of minocycline (C23H27N3O7) per mL. Use this solution within 3 hours.
Resolution solution— Transfer 10 mg of USP Minocycline Hydrochloride RS to a 25-mL volumetric flask, add 20 mL of 0.2 M ammonium oxalate, and swirl to dissolve. Heat on a water bath at 60 for 180 minutes, and allow to cool. Dilute with water to volume, and mix.
Assay preparation— Transfer an accurately weighed quantity of Minocycline Hydrochloride, equivalent to about 50 mg of minocycline (C23H27N3O7), to a 100-mL volumetric flask, add water 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 L1, and is maintained at a constant temperature of about 40. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, is not less than 5.0 and not more than 11.5; the tailing factor for the analyte peak is not less than 0.9 and not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%. Chromatograph the Resolution solution and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for epiminocycline and 1.0 for minocycline; and the resolution, R, between epiminocycline and minocycline is not less than 4.6.
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 µg per mg, of minocycline (C23H27N3O7), in the portion of Minocycline Hydrochloride taken by the formula:
100(C/W)(rU / rS),
in which C is the concentration, in µg per mL, of minocycline (C23H27N3O7) in the Standard preparation; W is the weight, in mg, of Minocycline Hydrochloride taken; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Brian D. Gilbert, Ph.D., Scientist
Expert Committee : (MDANT05) Monograph Development-Antibiotics
USP29–NF24 Page 1439
Pharmacopeial Forum : Volume No. 28(3) Page 770
Phone Number : 1-301-816-8223