(tye kloe' pi deen hye'' droe klor' ide).
Thieno[3,2-c]pyridine, 5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydro-, hydrochloride;
5-(o-Chlorobenzyl)-4,5,6,7-tetrahydrothieno-[3,2-c]pyridine hydrochloride [53885-35-1].
Ticlopidine Hydrochloride contains NLT 98.0% and NMT 102.0% of C14H14ClNS·HCl, calculated on the dried basis.
• B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
• C. Identification TestsGeneral, Chloride 191: Meets the requirements
Buffer: 1.1 g of monobasic sodium phosphate and 0.28 g of dibasic sodium phosphate in 1000 mL of water. The pH of solution is between 6.1 and 6.6. If necessary, adjust to the required pH using phosphoric acid or sodium hydroxide.
Mobile phase: Acetonitrile, methanol, and Buffer (6:7:7)
System suitability solution: 0.2 mg/mL of USP Ticlopidine Hydrochloride RS and 0.2 mg/mL of USP Sulconazole Nitrate RS in Mobile phase. [NoteSonication may be necessary for complete dissolution. ]
Standard solution: 0.4 mg/mL of USP Ticlopidine Hydrochloride RS in Mobile phase
Sample solution: 0.4 mg/mL of Ticlopidine Hydrochloride in Mobile phase
Detector: UV 215 nm
Column: 4.6-mm × 25-cm; 10-µm packing L7
Flow rate: 2 mL/min
Column temperature: 40
Run time: 1.5 times the retention time of the ticlopidine peak
Injection size: 10 µL
Samples: System suitability solution and Standard solution
Resolution: NLT 2.6 between ticlopidine hydrochloride and sulcanazole nitrate, System suitability solution
Relative standard deviation: NMT 1.0%, Standard solution
Samples: Standard solution and Sample solution
Calculate the percentage of C14H14ClNS·HCl in the portion of Ticlopidine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
• Residue on Ignition 231: NMT 0.1% on a 1-g sample
• Heavy Metals, Method I 231: NMT 20 ppm
• Procedure 1
Adsorbent: 0.25-mm thickness of silica
Developing solvent: Butanol, water, and glacial acetic acid (4:5:1). Shake well in a separatory funnel, allow it to settle, discard the lower aqueous layer, and use the upper organic layer.
Diluent: Methylene chloride and methanol (1:2)
Iodinemethanol reagent: Iodine TS and methanol (1:1)
Standard solution A: 15 mg/mL of USP Ticlopidine Hydrochloride RS in Diluent
Standard solution B: 2.5 mg/mL of each of USP Ticlopidine Related Compound A RS and USP Ticlopidine Related Compound B RS in Diluent
Sample solution: 15 mg/mL of Ticlopidine Hydrochloride in Diluent
Combined standard solution: Transfer 1.5 mL of Standard solution B and 250 µL of the Sample solution to a 25-mL volumetric flask and dilute to volume with Diluent.
Application size: 2, 5, and 10 µL of the Combined standard solution and 20 µL of the Sample solution
Samples: Sample solution and Combined standard solution
Develop the plate to a distance of at least 15 cm from the origin, and remove the plate and air dry for at least 1 h. Analyze visually under UV light. Estimate the amounts of ticlopidine related compound A and ticlopidine related compound B. Spray the plate with the Iodinemethanol reagent, and estimate any other impurities by comparing to the ticlopidine hydrochloride spots in the Combined standard solution.
• Procedure 2
Buffer, Mobile phase, System suitability solution, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.
Samples: Standard solution and Sample solution
Calculate the percentage of N-methyl ticlopidine in the portion of Ticlopidine Hydrochloride taken:
Result = (rU/rT) × 100
Calculate the percentage of any individual impurity in the portion of the Ticlopidine Hydrochloride taken:
Result = (rU/rS) × 100
• Loss on Drying 731: Dry a 1.0-g sample at 80 for 5 h: it loses NMT 1.0% of its weight.
• Limit of Formaldehyde
Mobile phase: Acetonitrile, water, and hydrochloric acid (3:2:0.004)
2,4 Dintirophenyl hydrazine solution: 1.65 mg/mL of 2,4-dinitrophenylhydrazine in acetonitrile
Standard stock solution: Transfer a known amount of formaldehyde solution, equivalent to 37 mg of formaldehyde, into a 100-mL volumetric flask. Dilute with methanol to volume.
Standard solution: Dilute the Standard stock solution with methanol to prepare a 1.85-µg/mL solution.
Sample solution: 0.50 g of Ticlopidine Hydrochloride in 10 mL methanol (sonication may be necessary for complete dissolution)
Derivatized standard and sample solutions: Transfer 2.0 mL of 2,4-Dinitrophenyl hydrazine solution to five different 10-mL volumetric flasks: 50 µL of 2 N hydrochloric acid and 150, 250, and 500 µL of the Standard solution to the first three flasks; 500 µL of the Sample solution to the fourth; and 500 µL of methanol to the fifth flask. Mix each solution well and allow the solutions to react for at least 30 min at ambient temperature. Dilute each flask with Mobile phase to volume and mix well. The solutions should be analyzed within 4 h.
Detector: UV 365 nm
Column: 4.6-mm × 15-cm; 5-µm packing L1
Flow rate: 1 mL/min
Injection size: 20 µL
Sample: Derivatized standard solution prepared from 500 µL
Relative standard deviation: NMT 10.0%
Samples: Derivatized standard solutions and Derivatized sample solution
[NoteThe approximate retention time for 2,4 dinitrophenylhydrazine is about 3.5 min and for the formaldehyde and 2,4 dinitrophenylhydrazine derivative is about 3.8 min. ]
Calculate the formaldehyde concentration in ppm in the Derivatized sample solution as the concentration in the Ticlopidine Hydrochloride taken:
Result = (C × D)/W
Formaldehyde: NMT 20 ppm
• Packaging and Storage: Preserve in tight containers, and store at a temperature below 30.
• USP Reference Standards 11
USP Ticlopidine Hydrochloride Related Compound A RS
USP Ticlopidine Hydrochloride Related Compound B RS
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 4865Pharmacopeial Forum: Volume No. 35(3) Page 582