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Trihexyphenidyl Hydrochloride
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C20H31NO·HCl 337.93

1-Piperidinepropanol, -cyclohexyl--phenyl-, hydrochloride, (±)-.
(±)--Cyclohexyl--phenyl-1-piperidinepropanol hydrochloride [52-49-3].
» Trihexyphenidyl Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C20H31NO·HCl, calculated on the dried basis.
Packaging and storage— Preserve in tight containers.
B: It responds to the tests for Chloride 191.
C: The retention time exhibited by trihexyphenidyl hydrochloride in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, as obtained in the Assay.
Loss on drying 731 Dry it at 105 for 3 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: 0.002%.
Chloride content— Dissolve about 1.2 g, accurately weighed, in a mixture consisting of 50 mL of methanol, 5 mL of glacial acetic acid, and 5 mL of water. Add 3 drops of eosin Y TS, and mix. Stir, preferably with a magnetic stirrer, and titrate with 0.1 N silver nitrate VS until the straw-orange suspension that forms during the titration changes sharply to red. Each mL of 0.1 N silver nitrate is equivalent to 3.545 mg of Cl. Not less than 10.3% and not more than 10.7% of Cl, calculated on the dried basis, is found.
Chromatographic purity—
Standard preparations— Dissolve USP Trihexyphenidyl Hydrochloride RS in a mixture of chloroform and isopropylamine (98:2), and mix to obtain a solution having a known concentration of 2.5 mg per mL. Dilute quantitatively with a mixture of chloroform and isopropylamine (98:2) to obtain Standard preparation A, containing 500 µg of the Reference Standard per mL, and Standard preparation B, containing 250 µg of the Reference Standard per mL.
Test preparation— Dissolve an accurately weighed quantity of Trihexyphenidyl Hydrochloride in a mixture of chloroform and isopropylamine (98:2) to obtain a solution containing 50 mg per mL.
Spray reagent— Dissolve 0.8 g of bismuth subnitrate in a mixture of 40 mL of water and 10 mL of glacial acetic acid (Solution A). Dissolve 8 g of potassium iodide in 20 mL of water (Solution B). On the day of use, mix equal volumes of Solution A and Solution B.
Procedure— Apply separately 10 µL of the Test preparation and 10 µL of each Standard preparation to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Position the plate in a chromatographic chamber, and develop the chromatograms in a solvent system consisting of a mixture of hexane and isopropylamine (98:2) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, allow the solvent to evaporate, and spray the plate, first with the Spray reagent, and then with sodium nitrite solution (4 in 100). Compare the intensities of any secondary spots observed in the chromatogram of the Test preparation with those of the principal spots in the chromatograms of the Standard preparations. No secondary spot from the chromatogram of the Test preparation is larger or more intense than the principal spot obtained from Standard preparation B (0.5%), and the sum of the intensities of all secondary spots obtained from the Test preparation corresponds to not more than 1.0%.
Organic volatile impurities, Method IV 467: meets the requirements.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Mobile phase— Prepare a mixture of acetonitrile, water, and triethylamine (920:80:0.2), adjust with phosphoric acid to a pH of 4.0, mix, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Trihexyphenidyl Hydrochloride RS in acetonitrile, and dilute quantitatively, and stepwise if necessary, with acetonitrile to obtain a solution having a known concentration of about 0.2 mg per mL.
Assay preparation— Transfer about 20 mg of Trihexyphenidyl Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dissolve in acetonitrile, dilute with acetonitrile to volume, and mix.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 210-nm detector and a 4.6-mm × 8-cm column that contains 3-µm packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency determined from the analyte peak is not less than 1300 theoretical plates, the tailing factor for the analyte peak is not more than 3.0, and the relative standard deviation for replicate injections is not more than 1.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C20H31NO·HCl in the portion of Trihexyphenidyl Hydrochloride taken by the formula:
100C(rU / rS),
in which C is the concentration, in mg per mL, of USP Trihexyphenidyl Hydrochloride RS in the Standard preparation, and rU and rS are the trihexyphenidyl peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Ravi Ravichandran, Ph.D., Senior Scientist
Expert Committee : (MDPP05) Monograph Development-Psychiatrics and Psychoactives
USP29–NF24 Page 2205
Phone Number : 1-301-816-8330