Thiethylperazine Maleate Suppositories
» Thiethylperazine Maleate Suppositories contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C22H29N3S2·2C4H4O4.
Packaging and storage— Preserve in tight containers at temperatures below 25. Do not expose unwrapped Suppositories to sunlight.
USP Reference standards 11
USP Thiethylperazine Maleate 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 using low-actinic glassware.
A: The retention time of the thiethylperazine peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation as obtained in the Assay.
B: The RF value of the principal spot and its color, as visualized by the spray reagents in the chromatogram of the Test solution, corresponds to that of Standard solution A as obtained in the test for Chromatographic purity.
Uniformity of dosage units 905: meet the requirements.
Chromatographic purity—
Diluent— Prepare a mixture of methanol, chloroform (stabilized with 0.75% alcohol), and ammonium hydroxide (55:45:1).
Standard solutions— Dissolve an accurately weighed quantity of USP Thiethylperazine Maleate RS in Diluent, and mix to obtain a solution having a known concentration of about 10 mg per mL. Dilute this solution quantitatively with Diluent to obtain Standard solutions, designated below by letter, having the following compositions:
Dilution Concentration
(µg RS
per mL)
Percentage (%,
for comparison
with test
A (1 in 20) 500 5
B (1 in 33) 300 3
C (1 in 50) 200 2
D (1 in 100) 100 1
E (1 in 200) 50 0.5
Test solution Transfer a number of Suppositories, equivalent to about 20 mg of thiethylperazine maleate, to a funnel having a fine porosity fritted disk. Add 50 mL of n-pentane, macerate, and mix with a glass stirring rod, collecting the filtrate in a filter flask under reduced pressure. Rinse the stirring rod and funnel with five 10-mL portions of n-pentane, and discard the filtrate. Transfer the funnel to a separate filter flask, add three 10-mL portions of Diluent, and collect the filtrate under reduced pressure. Evaporate the filtrate to dryness, add 2.0 mL of Diluent, and mix. Filter the resulting solution through a 0.45-µm filter, discarding the initial portion of the filtrate.
Procedure— Equilibrate for 3 hours a thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture in a solvent system consisting of methylene chloride, isopropyl alcohol, methanol, and ammonium hydroxide (85:15:2:1). Remove the plate from the chamber, and allow the solvent to evaporate. Separately apply 10 µL of the Test solution and 10 µL of each Standard solution to the plate, and develop the chromatogram in a separate lined chamber in the solvent system previously described 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, and allow to evaporate in a stream of nitrogen for about 10 minutes. Examine the plate under short- and long-wavelength UV light, and compare the intensities of any secondary spots observed in the chromatogram of the Test solution with those of the principal spots in the chromatograms of the Standard solutions. Spray the plate with Dragendorff's reagent followed by a 9% solution of hydrogen peroxide in water, and cover with a glass plate for 5 minutes. Remove the glass plate, and observe under white light. Record the RF values and estimate the concentration of the secondary spots observed in the Test solution. No secondary spot from the chromatogram of the Test solution observed, using the visualization methods above, is larger or more intense than the principal spot obtained from Standard solution E (0.5%), and the sum of the intensities of the secondary spots obtained from the Test solution corresponds to not more than 5%.
Mobile phase— Prepare a filtered and degassed mixture of methanol and 10% ammonium carbonate (9:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent— Prepare a mixture of methanol, chloroform, and ammonium hydroxide (55:45:1).
Standard preparation— Dissolve an accurately weighed quantity of USP Thiethylperazine Maleate RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 0.1 mg per mL.
Assay preparation— Weigh not fewer than 20 Suppositories and freeze them at 0 for about 30 minutes. Grind the Suppositories into small particles, and transfer an accurately weighed portion of the mass, equivalent to about 10 mg of thiethylperazine maleate, to a 100-mL volumetric flask. Add about 30 mL of Diluent, and gently shake for about 10 minutes or until the mass dissolves. Dilute with Diluent to volume, mix, and filter through about 2 g of anhydrous sodium sulfate, discarding the first portion of the filtrate.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 265-nm detector and a 4.6-mm × 25-cm column that contains 5-µm, base-deactivated packing L1. The flow rate is about 2 mL per minute, and the column temperature is maintained at 45. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between the thiethylperazine peak and adjacent peaks is not less than 1.0; the column efficiency is not less than 1000 theoretical plates; the tailing factor for thiethylperazine is not more than 2.5; and the relative standard deviation for replicate injections is not more than 2.0%.
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 C22H29N3S2·2C4H4O4 in the portion of Suppositories taken by the formula:
100C(rU / rS)
in which C is the concentration, in mg per mL, of USP Thiethylperazine Maleate RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Elena Gonikberg, Ph.D.
Senior Scientist
(MDGRE05) Monograph Development-Gastrointestinal Renal and Endocrine
Reference Standards Lili Wang, Technical Services Scientist
USP32–NF27 Page 3721
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.