Thioridazine 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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Thioridazine Hydrochloride contains NLT 99.0% and NMT 101.0% of thioridazine hydrochloride, calculated on the dried basis.

[Note—Throughout the following procedures, protect test or Assay samples, the Reference Standard, and solutions containing them, by conducting the analyses without delay, under subdued light, or by using low-actinic glassware.]

1 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

B. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride

Sample solution: 10 mg/mL in a mixture of water and alcohol (50:50)

Acceptance criteria: Meets the requirements of the test for amine hydrochlorides

2 ASSAY

Procedure

Solution A: Glacial acetic acid and acetic anhydride (50:50)

Sample solution: Dissolve 350 mg of Thioridazine Hydrochloride in 80 mL of Solution A.

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.1 N perchloric acid VS

Blank: Solution A

Endpoint detection: Potentiometric

Analysis

Samples: Sample solution and Blank

Titrate the Sample solution with Titrant. Perform a blank determination, and make any necessary correction.

Calculate the percentage of thioridazine hydrochloride in the portion of Thioridazine Hydrochloride taken:

Result = {[(V_S – V_B) × N_A × F]/W} × 100

V_S = Titrant volume consumed by the Sample solution (mL)

V_B = Titrant volume consumed by the Blank (mL)

N_A = normality of the Titrant (mEq/mL)

F = equivalency factor, 407.04 (mg/mEq)

W = sample weight (mg)

Acceptance criteria: 99.0%–101.0% on the dried basis

3 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Change to read:

Selenium 〈291〉, Procedures, Procedure 1 (CN 1-Jun-2023)

Sample: 100 mg of sample mixed with 100 mg of magnesium oxide

Acceptance criteria: NMT 30 ppm

Organic Impurities

Diluent: Methanol and ammonium hydroxide (98:2)

Standard solution: 20.0 mg/mL of USP Thioridazine Hydrochloride RS in Diluent

Comparison solution A: 0.01 mg/mL from Standard solution in Diluent (0.05%)

Comparison solution B: 0.02 mg/mL from Standard solution in Diluent (0.1%)

Comparison solution C: 0.025 mg/mL from Standard solution in Diluent (0.125%)

Comparison solution D: 0.067 mg/mL from Standard solution in Diluent (0.33%)

Comparison solution E: 0.1 mg/mL from Standard solution in Diluent (0.5%)

Sample solution: 20 mg/mL of Thioridazine Hydrochloride in Diluent

Chromatographic system

(See Chromatography 〈621〉, General Procedures, Thin-Layer Chromatography.)

Mode: TLC

Application volume: 5 μL

Developing solvent system: Chloroform, isopropyl alcohol, and ammonium hydroxide (74:25:1)

Spray reagent: Dragendorff's TS and Hydrogen peroxide TS

Analysis

Samples: Standard solution, Comparison solutions A–E, and Sample solution

Proceed as directed in 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 spray with hydrogen peroxide TS.

Acceptance criteria: Any secondary spot from the Sample solution is NMT 0.5%, and the sum of all secondary spots is NMT 0.5%.

4 SPECIFIC TESTS

Melting Range or Temperature 〈741〉: 159°–165°; the range between beginning and end of melting does not exceed 3°

pH 〈791〉

Sample solution: 10 mg/mL

Acceptance criteria: 4.2–5.2

Loss on Drying 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.4%

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Thioridazine Hydrochloride RS