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Thioridazine Hydrochloride
C21H26N2S2·HCl 407.04

10H-Phenothiazine, 10-[2-(1-methyl-2-piperidinyl)ethyl]-2-(methylthio)-, monohydrochloride.
10-[2-(1-Methyl-2-piperidyl)ethyl]-2-(methylthio)phenothiazine monohydrochloride [130-61-0].
» Thioridazine Hydrochloride contains not less than 99.0 percent and not more than 101.0 percent of C21H26N2S2·HCl, calculated on the dried basis.
Packaging and storage— Preserve in tight, light-resistant containers.
USP Reference standards 11— USP Thioridazine Hydrochloride RS.
NOTE—Throughout the following procedures, protect test or assay specimens, the Reference Standard, and solutions containing them, by conducting the procedures without delay, under subdued light, or by using low-actinic glassware.
Identification—
B: A solution (1 in 10) responds to the tests for Chloride 191.
Melting range 741: between 159 and 165, but the range between beginning and end of melting does not exceed 3.
pH 791: between 4.2 and 5.2, in a solution (1 in 100).
Loss on drying 731— Dry it at 105 for 4 hours: it loses not more than 0.4% of its weight.
Residue on ignition 281: not more than 0.1%.
Selenium 291: 0.003%, a 100-mg specimen being used, 100 mg of magnesium oxide being added to the Test Solution.
Chromatographic purity— [NOTE—Conduct this procedure in subdued lighting without delay.]
Diluting solution: a mixture of methanol and ammonium hydroxide (49:1).
Test solution— Transfer 100 mg of Thioridazine Hydrochloride, accurately weighed, to a 5-mL volumetric flask. Dissolve in and dilute with Diluting solution to volume, and mix.
Standard solutions— Dissolve an accurately weighed quantity of USP Thioridazine Hydrochloride RS in Diluting solution, and dilute quantitatively, and stepwise if necessary, with Diluting solution to obtain a solution having a known concentration of 20.0 mg per mL (Standard solution A). Dilute appropriate portions of this solution quantitatively with Diluting solution to obtain five Standard solutions B to F having known concentrations of 0.1, 0.067, 0.025, 0.02 and 0.01 mg per mL, respectively. The final concentrations of Standard solutions B to F represent 0.5%, 0.33%, 0.125%, 0.1% and 0.05% concentration of Standard solution A, respectively.
Application volume: 5 µL.
Developing solvent system: a mixture of chloroform, isopropyl alcohol, and ammonium hydroxide (74:25:1).
Procedure— Apply equal spots of the Test solution and Standard solutions A to F as directed under Ordinary Impurities 466. Examine the plate under short- and long-wavelength UV light, then spray the plate with Dragendorff's TS, dry the plate with a stream of nitrogen, and then spray with hydrogen peroxide TS: any secondary spot in the Test solution is not more than 0.5%, and the sum of all secondary spots is not more than 0.5%.
Organic volatile impurities, Method IV 467: meets the requirements.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 350 mg of Thioridazine Hydrochloride, accurately weighed, in 80 mL of a solution of equal parts of glacial acetic acid and acetic anhydride, and titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 40.70 mg of C21H26N2S2·HCl.
Auxiliary Information— Staff Liaison : Ravi Ravichandran, Ph.D., Senior Scientist
Expert Committee : (MDPP05) Monograph Development-Psychiatrics and Psychoactives
USP29–NF24 Page 2132
Pharmacopeial Forum : Volume No. 31(3) Page 798
Phone Number : 1-301-816-8330