Revision Bulletin
Official October 1, 2010
Tetracycline 1
Acceptance criteria: 90.0%–125.0%
Tetracycline Hydrochloride Capsules
PERFORMANCE TESTS
DEFINITION
Tetracycline Hydrochloride Capsules contain NLT 90.0% and
NMT 125.0% of the labeled amount of C22H24N2O8 · HCl.
Change to read:
.
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
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
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
System suitability
Samples: Standard solution and System suitability solution
[NOTE—The relative retention times of 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
rS
CS
CU
P
F
= peak response of tetracycline from the Sample
solution
= peak response of tetracycline from the Standard
solution
= concentration of USP Tetracycline Hydrochloride
RS in the Standard solution (mg/mL)
= nominal concentration of the Sample solution
(mg/mL)
= potency of USP Tetracycline Hydrochloride RS
(µg/mg)
= conversion factor, 0.001 mg/µg
• DISSOLUTION 〈711〉
•Test 1• (RB 1-Oct-2010)
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 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, preheated at 37.0 ± 0.5°.
Blank: Medium
Tolerances: See Tables 1 and 2.
Table 1
For Capsules Labeled to Contain 250 mg
Time (min)
Amount Dissolved
30
NLT 60% (Q)
60
NLT 85% (Q)
Table 2
For Capsules Labeled to Contain 500 mg
Time (min)
Amount Dissolved
30
NLT 50% (Q)
60
NLT 70% (Q)
90
NLT 85% (Q)
• (RB 1-Oct-2010)
• UNIFORMITY OF DOSAGE UNITS 〈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.
2010 The United States Pharmacopeial Convention All Rights Reserved.
2
Revision Bulletin
Official October 1, 2010
Tetracycline
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.
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight, light-resistant
containers.
Add the following:
••
LABELING: When more than one Dissolution test is
given, the labeling states the test used only if Test 1 is not
used.• (RB 1-Oct-2010)
• USP REFERENCE STANDARDS 〈11〉
USP 4-Epianhydrotetracycline Hydrochloride RS
2-Naphthacenecarboxamide, 4-(dimethylamino)1,4,4a,5,12,12a-hexahydro-3,10,11,12a-tetrahydroxy-6methyl-1,12-dioxo, monohydrochloride, [4R-(4α, 4aβ,
12aβ)]
C22H22N2O7 · HCl
462.89
USP Tetracycline Hydrochloride RS
(4S,4aS,5aS,6S,12aS)-4-(Dimethylamino)1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12apentahydroxy- 6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride.
C22H24N2O8 · HCl 480.90
2010 The United States Pharmacopeial Convention All Rights Reserved.