Tizanidine Hydrochloride

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₉H₈CIN₅S · HCI           290.17

2,1,3-Benzothiadiazol-4-amine, 5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-, monohydrochloride;

5-Chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazole monohydrochloride    CAS RN^®: 64461-82-1; UNII: B53E3NMY5C.

1 DEFINITION

Tizanidine Hydrochloride contains NLT 98.0% and NMT 102.0% of tizanidine hydrochloride (C₉H₈CIN₅S · HCI), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Change to read:

C. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests. Chloride

Sample solution: 10 mg/mL

Acceptance criteria: Meets the requirements ^▲_{▲(USP 1-May-2021)}

3 ASSAY

Change to read:

PROCEDURE

Buffer: 6.8 g/L of monobasic potassium phosphate. Adjust with 5.3 N potassium hydroxide to a pH of 7.5 ± 0.05.

Mobile phase: Acetonitrile and Buffer (20:80)

System suitability solution: 46 µg/mL of USP Tizanidine Hydrochloride RS and 0.12 µg/mL of USP Tizanidine Related Compound C RS in Mobile phase

Standard solution: 0.046 mg/mL of USP Tizanidine Hydrochloride RS in Mobile phase

Sample solution: 0.046 mg/mL of Tizanidine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm x 15-cm; packing L7

Column temperature: 35°

Flow rate: 1 mL/min

Injection volume: 20 µL

^▲Run time: NLT 2.3 times the retention time of tizanidine _{▲(USP 1-May-2021)}

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for tizanidine related compound C and tizanidine are 0.5 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 6 between tizanidine and tizanidine related compound C, System suitability solution

Tailing factor: NMT 2.0 for tizanidine, Standard solution

Relative standard deviation: NMT ^▲0.73% _{▲(USP 1-May-2021)} Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of tizanidine hydrochloride (C₉H₈CIN₅S · HCI) in the portion of Tizanidine Hydrochloride taken:

                          Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of tizanidine from the Sample solution

r_S = peak area of tizanidine from the Standard solution

C_S = concentration of USP Tizanidine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

Change to read:

4.2 ORGANIC IMPURITIES

Solution A: Water and phosphoric acid (88:12)

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 (20:80)

System suitability stock solution: 0.1 mg/mL each of USP Tizanidine Related Compound A RS. USP Tizanidine Related Compound B RS, and USP Tizanidine Related Compound C. RS in methanol

System suitability solution: 0.23 mg/mL of USP Tizanidine Hydrochloride RS, and 0.01 mg/mL each of USP Tizanidine Related Compound A RS, USP Tizanidine Related Compound B. RS, and USP Tizanidine Related Compound C. RS from System suitability stock solution in Mobile phase

Standard solution: 0.046 mg/mL of USP Tizanidine Hydrochloride RS in Mobile phase

Sample solution: 1.14 mg/mL of Tizanidine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm x 25-cm; packing L1

Column temperature: 50°

Flow rate: 1 mL/min

Injection volume: 10 µL

^▲Run time: NLT 11 times the retention time of tizanidine _{▲(USP 1-May-2021)}

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 4.0 between tizanidine and tizanidine related compound C; NLT 4.0 between tizanidine and tizanidine related compound B, System suitability solution

Column efficiency: NLT 5000 theoretical plates, Standard solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tizanidine Hydrochloride taken:

                          Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2)×(1/F) x 100

r_U = peak area of each impurity from the Sample solution

r_S = peak area of tizanidine from the Standard solution

C_S = concentration of USP Tizanidine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Tizanidine Hydrochloride in the Sample solution (mg/mL)

M_r1 = molecular weight of tizanidine, 253.71

M_r2 = molecular weight of tizanidine hydrochloride, 290.17 

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. ^▲Reporting threshold is 0.05%_{▲(USP 1-May-2021)}

Table 1

5 SPECIFIC TESTS

5.1 pH (791)

Sample solution: 10 mg/mL

Acceptance criteria: 4.3-5.3

5.2 LOSS ON DRYING (731)

Sample: 0.5 g

Analysis: Dry the Sample at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at room temperature.

Change to read:

USP REFERENCE STANDARDS (11)

USP Tizanidine Hydrochloride RS

USP Tizanidine Related Compound A RS

4-Amino-5-chloro-2,1,3-benzothiadiazole.

C₆H₄CIN₃S            185.63

USP Tizanidine Related Compound B RS

^▲5-Chloro-4-(1-acetyl-2-imidazolin-2-ylamino)-2,1,3-benzothiadiazole._{▲(USP 1-May-2021)}

C₁₁H₁₀CIN₅OS            295.75

USP Tizanidine Related Compound CRS

1-Acetylimidazolidine-2-thione.

C₅H₈N₂OS            ^▲144.19_{▲(USP 1-May-2021)}