Tizanidine Tablets
DEFINITION
Tizanidine Tablets contain Tizanidine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of tizanidine (C9H8ClN5S).
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
Solution A:
Water and phosphoric acid (44:6)
Buffer:
3.5 g/L of sodium 1-pentanesulfonate. Adjust with Solution A or 1 N sodium hydroxide to a pH of 3.0 ± 0.05.
Mobile phase:
Acetonitrile and Buffer (1:4)
Tizanidine related compound A solution:
0.1 mg/mL of USP Tizanidine Related Compound A RS in methanol
Tizanidine related compound B solution:
0.1 mg/mL of USP Tizanidine Related Compound B RS in methanol
Tizanidine related compound C solution:
0.1 mg/mL of USP Tizanidine Related Compound C RS in methanol
System suitability solution:
Transfer 23 mg of USP Tizanidine Hydrochloride RS to a 100-mL volumetric flask, add 20 mL of Mobile phase and 10 mL each of Tizanidine related compound A solution, Tizanidine related compound B solution, and Tizanidine related compound C solution. Sonicate to dissolve the USP Tizanidine Hydrochloride RS, and dilute with Mobile phase to volume.
Standard solution:
0.046 mg/mL of USP Tizanidine Hydrochloride RS in Mobile phase
Sample solution:
Transfer a weighed portion of finely powdered Tablets (NLT 20), equivalent to 20 mg of tizanidine, to a 500-mL volumetric flask. Add 250 mL of Buffer solution, sonicate for 15 min with occasional shaking, and shake by mechanical means for 15 min. Add 100 mL of acetonitrile, and mix. Allow to cool, and dilute with Buffer solution to volume. Centrifuge a portion of this solution at 2000 rpm or higher for 10 min. Pass a portion of this solution through a filter having a 0.45-µm or finer pore size, and use the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
4.6-mm × 25-cm; packing L1
Temperature:
Column is maintained at 50
.
.
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Suitability requirements
Resolution:
NLT 4.0 between tizanidine and tizanidine related compound C; NLT 4.0 between tizanidine and tizanidine related compound B
Column efficiency:
NLT 5000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C9H8ClN5S in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Tizanidine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of tizanidine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of tizanidine, 253.71 |
| Mr2 | = | = molecular weight of tizanidine hydrochloride, 290.17 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Test 1
Medium:
0.1 N hydrochloric acid; 500 mL
Apparatus 1:
100 rpm
Time:
15 min
Sample solution:
Sample per Dissolution 711. Dilute with Medium to a concentration that is similar to the Standard solution.
711. Dilute with Medium to a concentration that is similar to the Standard solution.
Solution A, Buffer, and Mobile phase:
Proceed as directed in the Assay.
Standard solution:
(L/500) mg/mL of USP Tizanidine Hydrochloride RS in Medium, where L is the label claim in mg
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
4.6-mm × 25-cm; packing L1
Column temperature:
50
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 2000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C9H8ClN5S dissolved:
Result = (rU/rS) × CS × V × (1/L) × (Mr1/Mr2) × 100
| rU | = | = peak response of tizanidine from the Sample solution |
| rS | = | = peak response of tizanidine from the Standard solution |
| CS | = | = concentration of USP Tizanidine Hydrochloride RS in the Standard solution (mg/mL) |
| V | = | = volume of dissolution Medium, 500 mL |
| L | = | = label claim in mg |
| Mr1 | = | = molecular weight of tizanidine, 253.71 |
| Mr2 | = | = molecular weight of tizanidine hydrochloride 290.17 |
Tolerances:
NLT 80% (Q) of the labeled amount of C9H8ClN5S is dissolved.
Test 2
[Note—If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2. ]
Medium:
0.1 N hydrochloric acid; 500 mL, deaerated
Apparatus 1:
100 rpm
Time:
30 min
Standard solution:
(L/500) mg/mL of USP Tizanidine Hydrochloride RS in Medium, where L is the label claim in mg
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
228 nm
Cell:
1.0 cm
Blank:
Medium
Analysis
Samples:
Standard solution, Sample solution, and Blank
Calculate the percentage of tizanidine dissolved:
Result = (AU/AS) × CS × V × (1/L) × (Mr1/Mr2) × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of USP Tizanidine Hydrochloride RS in the Standard solution (mg/mL) |
| V | = | = volume of dissolution Medium, 500 mL |
| L | = | = label claim in mg |
| Mr1 | = | = molecular weight of tizanidine, 253.71 |
| Mr2 | = | = molecular weight of tizanidine hydrochloride, 290.17 |
Tolerances:
NLT 80% (Q) of the labeled amount of tizanidine is dissolved.
IMPURITIES
Organic Impurities
• Procedure
Solution A, Buffer, Mobile phase, and Standard solution:
Proceed as directed in the Assay.
Sample solution:
Transfer a weighed portion of finely powdered Tablets (NLT 20), equivalent to 20 mg of tizanidine, to a 100-mL volumetric flask. Add about 50 mL of Buffer solution, sonicate for about 15 min with occasional shaking, and shake by mechanical means for 15 min. Add 20 mL of acetonitrile, and mix. Allow to cool, dilute with Buffer solution to volume, and mix. Centrifuge a portion of this solution at 2000 rpm or higher for 10 min. Pass a portion of this solution through a filter having a 45-µm or finer pore size, and use the filtrate.
Chromatographic system and System suitability:
Proceed as directed in the Assay.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × F × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of tizanidine from the Standard solution |
| CS | = | = concentration of USP Tizanidine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of tizanidine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of tizanidine, 253.71 |
| Mr2 | = | = molecular weight of tizanidine hydrochloride, 290.17 |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.5 %
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Tizanidine related compound C | About 0.8 | 1.0 | 0.2 |
| Tizanidine | 1.0 | — | — |
| Tizanidine related compound B | About 1.4 | 0.9 | 0.2 |
| Tizanidine related compound A | About 10.2 | 0.9 | 0.2 |
| Individual unidentified impurity | — | 1.0 | 0.2 |
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers, and store at controlled room temperature.
• 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 Tizanidine Hydrochloride RS
USP Tizanidine Related Compound A RS
4-Amino-5-chloro-2,1,3-benzothiadiazole.
C6H4ClN3S 185.63
4-Amino-5-chloro-2,1,3-benzothiadiazole.
C6H4ClN3S 185.63
USP Tizanidine Related Compound B RS
N-Acetyltizanidine.
C11H10ClN5OS 295.75
N-Acetyltizanidine.
C11H10ClN5OS 295.75
USP Tizanidine Related Compound C RS
1-Acetylimidazolidine-2-thione.
C5H8N2OS 144.20
1-Acetylimidazolidine-2-thione.
C5H8N2OS 144.20
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| 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 4878
Pharmacopeial Forum: Volume No. 35(3) Page 585