» Pindolol Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of pindolol (C14H20N2O2).
Packaging and storage Preserve in well-closed containers, protected from light.
USP Reference standards 11
A: Examine the chromatograms obtained in the test for Chromatographic purity: the principal spot obtained from the Test solution is similar in RF value, color, and intensity to that obtained from the Standard stock solution.
B: The retention time exhibited by pindolol in the chromatogram of the Assay preparation corresponds to that of pindolol in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution, Procedure for a Pooled Sample 711
Medium: 0.1 N hydrochloric acid; 500 mL.
Apparatus 2: 50 rpm.
Time: 15 minutes.
Mobile phase and Chromatographic systemProceed as directed in the Assay.
Standard solution Dissolve an accurately weighed quantity of USP Pindolol RS in Dissolution Medium to obtain a solution having a known concentration of about 0.002J mg per mL, J being the labeled quantity, in mg, of pindolol in each Tablet. Mix equal volumes of this solution and of Mobile phase to obtain the Standard solution.
Resolution solution Dissolve a quantity of nortriptyline hydrochloride in Standard solution to obtain a solution having a concentration of about 0.005 mg of nortriptyline hydrochloride per mL.
Test solution Filter a portion of the solution under test. Mix equal volumes of the filtrate and of Mobile phase to obtain the Test solution.
Procedure Proceed as directed for Procedure under the Assay. Calculate the quantity of C14H20N2O2 dissolved by the formula:
500C(rU / rS)in which C is the concentration, in mg per mL, of USP Pindolol RS in the Standard solution; and rU and rS are the pindolol peak responses obtained from the Test solution and the Standard solution, respectively.
Tolerances Not less than 80% (Q) of the labeled amount of C14H20N2O2 is dissolved in 15 minutes.
Uniformity of dosage units 905: meet the requirements.
Chromatographic purity [noteProtect solutions and chromatographic plate (after application of solutions) from light. ]
p-Dimethylaminobenzaldehyde spray Dissolve 1 g of p-dimethylaminobenzaldehyde in a mixture of 50 mL of hydrochloric acid and 50 mL of alcohol, and mix. [noteStore this solution in a tightly closed, light-resistant container, and discard after 4 weeks. ]
Solvent mixture Prepare a solution of methanol and glacial acetic acid (99:1).
Standard stock solution Dissolve an accurately weighed quantity of USP Pindolol RS in Solvent mixture to obtain a solution containing 5.0 mg per mL.
Standard solution 1 Dilute an accurately measured volume of Standard stock solution quantitatively and stepwise with Solvent mixture to obtain a solution containing 0.025 mg per mL.
Standard solution 2 Dilute 6.0 mL of Standard solution 1 with Solvent mixture to 10.0 mL, and mix.
Standard solution 3 Dilute 4.0 mL of Standard solution 1 with Solvent mixture to 10.0 mL, and mix.
Standard solution 4 Dilute 2.0 mL of Standard solution 1 with Solvent mixture to 10.0 mL, and mix.
Test solution [notePrepare this solution immediately before use, and apply last. ] Transfer a portion of powdered Tablets, equivalent to 50 mg of pindolol, to a 50-mL flask, add 10.0 mL of Solvent mixture, insert the stopper in the flask, and shake by mechanical means for 15 minutes. Centrifuge a portion of the resultant suspension, and promptly test the clear supernatant.
Procedure Prepare a lined chromatographic chamber (see Chromatography 621) with a developing solvent consisting of a mixture of methylene chloride, methanol, and formic acid (75:23.5:1.5), and equilibrate for 30 minutes. Separately apply 2-µL portions of the Standard stock solution, each of the Standard solutions, and the Test solution to a thin-layer chromatographic plate coated with a 0.25-mm layer of chromatographic silica gel. Place the plate in the chromatographic chamber, and allow the solvent front to move about two-thirds of the length of the plate. Remove the plate from the chamber, immediately spray with the p-Dimethylaminobenzaldehyde spray, heat the plate at 60 for 15 minutes, and promptly examine the chromatogram: no individual secondary spot observed in the chromatogram of the Test solution is greater in size or intensity than the principal spot observed in the chromatogram of Standard solution 1, corresponding to 0.5%, and the total of any such spots observed does not exceed 3.0%. [noteIn a valid determination, spots from all solutions must be visible. ]
Ammonium carbonate solution Dissolve 300 mg of ammonium carbonate in 50 mL of water, and mix.
Mobile phase Prepare a filtered and degassed mixture of acetonitrile, methanol, and Ammonium carbonate solution (475:475:50), making adjustments, if necessary (see System Suitability under Chromatography 621).
Standard preparation Prepare a solution of USP Pindolol RS in Mobile phase to obtain a solution having a known concentration of about 0.2 mg per mL.
Resolution solution Dissolve a quantity of nortriptyline hydrochloride in Standard preparation to obtain a solution having a concentration of about 0.2 mg of nortriptyline hydrochloride per mL.
Assay preparation Weigh and finely powder not less than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 20 mg of pindolol, to a 100-mL volumetric flask. Add 4 mL of water, and sonicate for 2 minutes, with occasional shaking to disperse the powder. Add 30 mL of Mobile phase, sonicate for 15 minutes, and allow to cool. Dilute with Mobile phase to volume, mix, and filter. Use the clear filtrate as the Assay preparation.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L16. The flow rate is about 3 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution between pindolol and nortriptyline is not less than 1.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: 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. The relative retention times are about 0.6 for pindolol and 1.0 for nortriptyline. Calculate the quantity, in mg, of pindolol (C14H20N2O2) in the portion of Tablets taken by the formula:
100C(rU / rS)in which C is the concentration, in mg per mL, of USP Pindolol RS in the Standard preparation; and rU and rS are the pindolol peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 4328Pharmacopeial Forum: Volume No. 30(1) Page 165