Identification—
Transfer a quantity of powdered Tablets,equivalent to about 50mg of nadolol,to a conical flask.Add 10mLof 0.1Nhydrochloric acid,stir for 30minutes,using a magnetic stirrer,and place in an ultrasonic bath for an additional 30minutes.Centrifuge,and use the supernatant for the test solution.Apply,as streaks,100µLof the test solution and 100µLof a Standard solution of
USP Nadolol RSin 0.1Nhydrochloric acid having a concentration of about 5mg per mLto a thin-layer chromatographic plate (see
Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatogram in a solvent system consisting of acetone,chloroform,and 2Nammonium hydroxide (8:1:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,allow the solvent to evaporate,and examine the chromatogram under short-wavelength UVlight:the
RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
Dissolution á711ñ—
Medium:
0.01Nhydrochloric acid;900mL.
Apparatus 1:
100rpm.
Time:
50minutes.
Procedure—
Determine the amount of C
17H
27NO
4dissolved,employing the procedure set forth in the
Assay,except to prepare the
Mobile phaseusing 560mLof methanol and 1440mLof water instead of 700mLand 1300mL,respectively,and adjusting with 0.1Nhydrochloric acid to a pHof 2.5.Use filtered portions of the solution under test,suitably diluted with
Dissolution Medium,if necessary,in comparison with a Standard solution having a known concentration of
USP Nadolol RSin the same
Medium.
Tolerances—
Not less than 80%(Q)of the labeled amount of C17H27NO4is dissolved in 50minutes.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of 700mLof methanol and 1300mLof water containing 5.84g of sodium chloride and 1.0mLof 0.1Nhydrochloric acid.
Standard preparation—
Dissolve an accurately weighed quantity of
USP Nadolol RSin
Mobile phaseto obtain a solution having a known concentration of about 0.2mg per mL.
Assay preparation—
Weigh and finely powder not less than 20Tablets.Weigh accurately a portion of the powder,equivalent to about 20mg of nadolol,and transfer to a 100-mLvolumetric flask.Add about 75mLof Mobile phase,place in an ultrasonic bath for 15minutes,shaking intermittently,add Mobile phaseto volume,and mix.Clarify the solution by filtration or centrifugation.
Chromatographic system
(see
Chromatography á621ñ)—The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm ×25-cm column that contains packing L16.The flow rate is about 1mLper minute.Chromatograph 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 nadolol peak is not more than 3.
Procedure—
Separately inject equal volumes (about 20µL)of the
Standard preparationand the
Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of nadolol (C
17H
27NO
4)in the portion of Tablets taken by the formula:
100C(rU/rS),
in which
Cis the concentration,in mg per mL,of
USP Nadolol RSin the
Standard preparation;and
rUand
rSare the peak responses obtained from the
Assay preparationand the
Standard preparation,respectively.