(tet'' ra sye' kleen hye'' droe klor' ide).
2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, monohydrochloride, [4S-(4,4a,5a,6,12a)]-.
(4S,4aS,5aS,6S,12aS)-4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy- 6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride [64-75-5].
» Tetracycline Hydrochloride has a potency of not less than 900 µg of C22H24N2O8·HCl per mg.
Packaging and storage Preserve in tight, light-resistant containers.
Labeling Where it is intended for use in preparing injectable or other sterile dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable or other sterile dosage forms.
USP Reference standards 11
USP 4-Epianhydrotetracycline Hydrochloride RS
USP Endotoxin RS
A: Infrared Absorption 197KDo not dry specimen.
B: Ultraviolet Absorption 197U
Solution: 20 µg per mL.
Medium: 0.25 N sodium hydroxide.
Absorptivity 6 minutes after preparation, calculated on the dried basis, at 380 nm is between 96.0% and 104.0% of that of USP Tetracycline Hydrochloride RS, the potency of the Reference Standard being taken into account.
C: The chromatogram of the Assay preparation obtained as directed in the Assay exhibits a major peak for tetracycline, the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparation obtained as directed in the Assay.
D: To 0.5 mg add 2 mL of sulfuric acid: a purplish red color is produced. Add the solution to 1 mL of water: the color becomes yellow.
E: Prepare a Test Solution in methanol containing 1 mg per mL, and proceed as directed for Method II under IdentificationTetracyclines 193.
F: It responds to the silver nitrate test for Chloride 191.
Crystallinity 695: meets the requirements.
pH 791: between 1.8 and 2.8, in a solution containing 10 mg per mL.
Specific rotation 781: between 240 and 255, calculated on the dried basis.
Test solution: 5 mg per mL, in 0.1 N hydrochloric acid.
Loss on drying 731 Dry about 100 mg, accurately weighed, in a capillary-stoppered bottle in vacuum at a pressure not exceeding 5 mm of mercury at 60 for 3 hours: it loses not more than 2.0% of its weight.
Heavy metals, Method II 231: 0.005%.
Limit of 4-epianhydrotetracycline Using the Diluting solvent, Chromatographic system, and Procedure set forth in the Assay, chromatograph a Standard solution prepared by dissolving an accurately weighed quantity of USP 4-Epianhydrotetracycline Hydrochloride RS in Diluting solvent to obtain a solution having a known concentration of about 10 µg per mL. Using the chromatogram so obtained and the chromatogram of the Assay preparation obtained as directed in the Assay, calculate the percentage of 4-epianhydrotetracycline hydrochloride in the Tetracycline Hydrochloride taken by the formula:
10(CE / W)(rU / rS)in which CE is the concentration, in µg per mL, of USP 4-Epianhydrotetracycline Hydrochloride RS in the Standard solution; W is the weight, in mg, of Tetracycline Hydrochloride taken to prepare the Assay preparation; and rU and rS are the 4-epianhydrotetracycline peak responses obtained from the Assay preparation and the Standard solution, respectively: not more than 2.0% is found.
Other requirements Where the label states that Tetracycline Hydrochloride is sterile, it meets the requirements for Sterility and Bacterial endotoxins under Tetracycline Hydrochloride for Injection. Where the label states that Tetracycline Hydrochloride must be subjected to further processing during the preparation of injectable dosage forms, it meets the requirements for Bacterial endotoxins under Tetracycline Hydrochloride for Injection. Where it is intended for use in preparing nonparenteral sterile dosage forms, it is exempt from the requirements for Bacterial endotoxins.
Diluting solvent Mix 680 mL of 0.1 M ammonium oxalate and 270 mL of dimethylformamide.
Mobile phase Mix 680 mL of 0.1 M ammonium oxalate, 270 mL of dimethylformamide, and 50 mL of 0.2 M dibasic ammonium phosphate. Adjust, if necessary, with 3 N ammonium hydroxide or 3 N phosphoric acid to a pH of 7.6 to 7.7. Make any other necessary adjustments (see System Suitability under Chromatography 621). Filter through a membrane filter of 0.5-µm or finer porosity.
Standard preparation Dissolve an accurately weighed quantity of USP Tetracycline Hydrochloride RS in Diluting solvent, and dilute quantitatively with Diluting solvent to obtain a solution having a known concentration of about 0.5 mg per mL.
Assay preparation Transfer about 50 mg of Tetracycline Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dissolve in Diluting solvent, dilute with the same solvent to volume, and mix.
Resolution solution Prepare a solution in Diluting solvent containing about 100 µg of tetracycline hydrochloride and 25 µg of USP 4-Epianhydrotetracycline Hydrochloride RS per mL.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 280-nm detector, a 4.6-mm × 3-cm guard column that contains 10-µm packing L7, and a 4.6-mm × 25-cm analytical column that contains 5- to 10-µm packing L7. The flow rate is about 2 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.9 for 4-epianhydrotetracycline and 1.0 for tetracycline; and the resolution, R, between the 4-epianhydrotetracycline and tetracycline peaks is not less than 1.2. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: 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 the major peaks. Calculate the quantity, in µg, of C22H24N2O8·HCl in each mg of the Tetracycline Hydrochloride taken by the formula:
100(CP / W)(rU / rS)in which C is the concentration, in mg per mL, of USP Tetracycline Hydrochloride RS in the Standard preparation; P is the potency, in µg per mg, of USP Tetracycline Hydrochloride RS; W is the weight, in mg, of Tetracycline Hydrochloride taken to prepare the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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