Timolol Maleate Tablets
»Timolol Maleate Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of C13H24N4O3S·C4H4O4.
Packaging and storage— Preserve in well-closed containers.
Identification— Transfer a portion of powdered Tablets,equivalent to about 30mg of timolol maleate,to a 50-mLvolumetric flask,add about 2mLof 0.1Nhydrochloric acid,and shake gently.Add about 30mLof methanol,agitate for 20minutes,add methanol to volume,mix,and centrifuge.Similarly prepare a Standard solution containing 0.6mg of USP Timolol Maleate RSper mL.Separately apply 10µLof the test solution and 10µLof the Standard solution to a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatogram using a solvent system consisting of a mixture of chloroform,methanol,and ammonium hydroxide (80:20:1)until the solvent front has moved about three-fourths of the length of the plate.Air-dry,and examine under short-wavelength UVlight:the RFvalues of the principal spots obtained from the test solution correspond to those obtained from the Standard solution.
Dissolution,Procedure for a Pooled Sample á711ñ—
Medium: 0.1Nhydrochloric acid;500mL.
Apparatus 1: 100rpm.
Time: 20minutes.
Procedure— Determine the amount of timolol maleate in solution in filtered portions of the solution under test,in comparison with a Standard solution having a known concentration of USP Timolol Maleate RSin the same medium,employing the procedure set forth in the Assay,making any necessary modifications.
Tolerances— Not less than 80%(Q)of the labeled amount of timolol maleate (C13H24N4O3S·C4H4O4)is dissolved in 20minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Assay—
pH2.8phosphate buffer— Transfer 22.08g of monobasic sodium phosphate to a 2-liter volumetric flask,dilute with water to volume,adjust with phosphoric acid to a pHof 2.8±0.05,and filter.
Mobile phase— Prepare a suitable degassed and filtered mixture of pH2.8phosphate bufferand methanol (3:2).
Standard preparation— Transfer about 50mg of USP Timolol Maleate RS,accurately weighed,to a 500-mLvolumetric flask.Add 50mLof 0.05Mmonobasic sodium phosphate.Sonicate until the standard is dissolved,add 100mLof acetonitrile,shake,dilute with water to volume,and mix.
Assay preparation— Weigh and finely powder not less than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 10mg of timolol maleate,to a 100-mLvolumetric flask,add 10mLof 0.05Mmonobasic sodium phosphate,sonicate for 5minutes,and add 20mLof acetonitrile.Sonicate for 5minutes,add 20mLof water,shake for 10minutes,dilute with water to volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 295-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.8mLper minute.Chromatograph five replicate injections of the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 2.0%,and the tailing factor for the main peak is not greater than 2.0.
Procedure— Separately inject equal volumes (about 15µL)of the Standard preparationand the Assay preparationinto the chromatograph by means of a suitable microsyringe or sampling valve,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C13H24N4O3S·C4H4O4in the portion of Tablets taken by the formula:
100C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Timolol Maleate RSin the Standard preparation,and rUand rSare the peak responses obtained for timolol maleate from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1934
Pharmacopeial Forum:Volume No.30(1)Page 191
Phone Number:1-301-816-8305