Tetracycline Hydrochloride Capsules
DEFINITION
Tetracycline Hydrochloride Capsules contain NLT 90.0% and NMT 125.0% of the labeled amount of tetracycline hydrochloride (C22H24N2O8·HCl).
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Diluent:
Dimethylformamide and 0.1 M ammonium oxalate (27:68)
Mobile phase:
Dimethylformamide, 0.1 M ammonium oxalate, and 0.2 M dibasic ammonium phosphate (27:68:5). Adjust, if necessary, with 3 N ammonium hydroxide or 3 N phosphoric acid to a pH of 7.6–7.7.
Standard solution:
0.5 mg/mL of USP Tetracycline Hydrochloride RS in Diluent
Sample solution:
Equivalent to 0.5 mg/mL of tetracycline hydrochloride in Diluent from NLT 20 Capsules. [Note—Sonicate if necessary to dissolve. ]
System suitability solution:
100 µg/mL of tetracycline hydrochloride and 25 µg/mL of USP 4-Epianhydrotetracycline Hydrochloride RS in Diluent
Chromatographic system
Mode:
LC
Detector:
UV 280 nm
Guard column:
4.6-mm × 3-cm; 10-µm packing L7
Column:
4.6-mm × 25-cm; 5- to 10-µm packing L7
Flow rate:
2 mL/min
Injection volume:
20 µL
System suitability
Samples:
Standard solution and System suitability solution
[Note—The relative retention times for 4-epianhydrotetracycline and tetracycline are 0.9 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 1.2 between the 4-epianhydrotetracycline and tetracycline peaks, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of tetracycline hydrochloride (C22H24N2O8·HCl) in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × P × F × 100
| rU | = | = peak response of tetracycline from the Sample solution |
| rS | = | = peak response of tetracycline from the Standard solution |
| CS | = | = concentration of USP Tetracycline Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of the Sample solution (mg/mL) |
| P | = | = potency of USP Tetracycline Hydrochloride RS (µg/mg) |
| F | = | = conversion factor, 0.001 mg/µg |
Acceptance criteria:
90.0%–125.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Test 1
Medium:
Water; 900 mL
Apparatus 2:
75 rpm; maintain a distance of 45 ± 5 mm between the blade and the inside bottom of the vessel.
Time:
60 min; 90 min for 500-mg Capsules
Detector:
UV 276 nm
Standard solution:
USP Tetracycline Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter.
Analysis:
Determine the amount of tetracycline hydrochloride (C22H24N2O8·HCl) dissolved by using UV absorption on portions of the Sample solution suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Tetracycline Hydrochloride RS.
Tolerances:
NLT 80% (Q) of C22H24N2O8·HCl is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium:
Water; 900 mL, deaerated
Apparatus 2:
75 rpm; maintain a distance of 45 ± 5 mm between the blade and the inside bottom of the vessel.
Time
For Capsules labeled to contain 250 mg: 30 and 60 min
For Capsules labeled to contain 500 mg: 30, 60, and 90 min
Detector:
UV 276 nm
Standard solution:
USP Tetracycline Hydrochloride RS in Medium
Sample solution:
At the times specified, withdraw a known volume of the solution under test, and pass it through a suitable filter. Dilute with Medium, if necessary. Replace the volume withdrawn with the same amount of Medium, pre-heated at 37.0 ± 0.5
.
.
Blank:
Medium
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure: Limit of 4-Epianhydrotetracycline
Diluent, Mobile phase, Sample solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Standard solution:
10 µg/mL of USP 4-Epianhydrotetracycline Hydrochloride RS in Diluent
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of 4-epianhydrotetracycline hydrochloride in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × F × 100
| rU | = | = peak response of 4-epianhydrotetracycline from the Sample solution |
| rS | = | = peak response of 4-epianhydrotetracycline from the Standard solution |
| CS | = | = concentration of USP 4-Epianhydrotetracycline Hydrochloride RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of tetracycline hydrochloride in the Sample solution (mg/mL) |
| F | = | = conversion factor, 0.001 mg/µg |
Acceptance criteria:
NMT 3.0%
SPECIFIC TESTS
• Loss on Drying 731:
Dry 100 mg of Capsule contents in a capillary-stoppered bottle in vacuum at a pressure not exceeding 5 mm of mercury at 60 for 3 h: it loses NMT 4.0% of its weight.
731:
Dry 100 mg of Capsule contents in a capillary-stoppered bottle in vacuum at a pressure not exceeding 5 mm of mercury at 60 for 3 h: it loses NMT 4.0% of its weight.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers.
• Labeling:
When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.
• USP Reference Standards 11
11
USP 4-Epianhydrotetracycline Hydrochloride RS
2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,12,12a-hexahydro-3,10,11,12a-tetrahydroxy-6-methyl-1,12-dioxo, monohydrochloride, [4R-(4
, 4a
, 12a)].
C22H22N2O7·HCl 462.89
2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,12,12a-hexahydro-3,10,11,12a-tetrahydroxy-6-methyl-1,12-dioxo, monohydrochloride, [4R-(4
, 4a, 12a)].
C22H22N2O7·HCl 462.89
USP Tetracycline Hydrochloride RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ahalya Wise, M.S.
Senior Scientific Liaison 1-301-816-8161 |
(SM12010) Monographs - Small Molecules 1 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4811