Minocycline Hydrochloride
C23H27N3O7·HCl 493.94
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].
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C23H27N3O7·HCl 493.94
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].DEFINITION
Minocycline Hydrochloride contains the equivalent of NLT 890 µg and NMT 950 µg of minocycline (C23H27N3O7) per mg, calculated on the anhydrous basis.
IDENTIFICATION
• Infrared Absorption 
197K
:
Dry the Standard and Sample at 100
for 2 h before use.
197K:
Dry the Standard and Sample at 100 for 2 h before use.
ASSAY
• Procedure
[Note—Protect the Standard solution and Sample solution from light, store in a refrigerator, and use within 3 h. ]
Mobile phase:
Dimethylformamide, tetrahydrofuran, 0.2 M ammonium oxalate, and 0.01 M edetate disodium (120:80:600:180). Adjust with ammonium hydroxide to a pH of 7.2.
System suitability solution:
Dissolve 10 mg of USP Minocycline Hydrochloride RS in 20 mL of 0.2 M ammonium oxalate. Heat on a water bath at 60 for 3 h, allow to cool, and dilute with water to 25.0 mL.
for 3 h, allow to cool, and dilute with water to 25.0 mL.
Standard solution:
Equivalent to 500 µg/mL of minocycline (C23H27N3O7) from USP Minocycline Hydrochloride RS in water
Sample solution:
Equivalent to 500 µg/mL of minocycline (C23H27N3O7) from Minocycline Hydrochloride in water
Chromatographic system
Mode:
LC
Detector:
UV 280 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for epiminocycline and minocycline are 0.7 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 4.6 between epiminocycline and minocycline, System suitability solution
Tailing factor:
0.9–2.0 for the analyte peak, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the quantity, in µg/mg, of minocycline (C23H27N3O7) in the portion of Minocycline Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × P
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of minocycline in the Standard solution (µg/mL) |
| CU | = | = concentration of the Sample solution (µg/mL) |
| P | = | = potency of USP Minocycline Hydrochloride RS (µg/mg) |
Acceptance criteria:
890–950 µg/mg on the anhydrous basis
IMPURITIES
Organic Impurities
• Procedure
Mobile phase and System suitability solution:
Proceed as directed in the Assay
[Note—Protect the Sample solutions from light, store in a refrigerator, and use within 3 h. ]
Sample solution 1:
0.25 mg/mL of Minocycline Hydrochloride
Sample solution 2:
5 µg/mL of Minocycline Hydrochloride in water
Sample solution 3:
3 µg/mL of Minocycline Hydrochloride in water
Chromatographic system:
Proceed as directed in the Assay.
Run time:
2.6 times the retention time of minocycline, Sample solution 1
Analysis
Samples:
Sample solution 1, Sample solution 2, and Sample solution 3
Calculate the percentage of epiminocycline in the portion of Minocycline Hydrochloride taken:
Result = (rE1/rM3) × D1 × 100
| rE1 | = | = peak response of epiminocycline from Sample solution 1 |
| rM3 | = | = peak response of minocycline from Sample solution 3 |
| D1 | = | = dilution factor for Sample solution 3 |
Calculate the total percentage of impurities other than epiminocycline in the portion of Minocycline Hydrochloride taken:
Result = (rT/rM2) × D2 × 100
| rT | = | = sum of peak responses of all impurities other than epiminocycline from Sample solution 1 |
| rM2 | = | = peak response of minocycline from Sample solution 2 |
| D2 | = | = dilution factor for Sample solution 2 |
Acceptance criteria
Individual impurities:
NMT 1.2% epiminocycline
Total impurities (excluding epiminocycline):
NMT 2.0%
SPECIFIC TESTS
• Crystallinity 695:
Meets the requirements
695:
Meets the requirements
• pH 791:
3.5–4.5, in a solution equivalent to 10 mg/mL of minocycline
791:
3.5–4.5, in a solution equivalent to 10 mg/mL of minocycline
• Water Determination, Method I 921:
4.3%–8.0%
921:
4.3%–8.0%
• Sterility Tests 71:
Where the label states that Minocycline Hydrochloride is sterile, it meets the requirements.
71:
Where the label states that Minocycline Hydrochloride is sterile, it meets the requirements.
• Bacterial Endotoxins Test 85:
Where the label states that Minocycline Hydrochloride is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 1.25 USP Endotoxin Units/mg of minocycline.
85:
Where the label states that Minocycline Hydrochloride is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 1.25 USP Endotoxin Units/mg of minocycline.
ADDITIONAL REQUIREMENTS
• 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.
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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 |
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3926
Pharmacopeial Forum: Volume No. 36(2) Page 418