Nortriptyline Hydrochloride Capsules
»Nortriptyline Hydrochloride Capsules contain nortriptyline hydrochloride equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amount of nortriptyline (C19H21N).
Packaging and storage— Preserve in tight containers.
A: Transfer the contents of Capsules,equivalent to about 50mg of nortriptyline hydrochloride,to a suitable flask.Add 15mLof chloroform,insert the stopper in the flask,and shake for 15minutes.Transfer the mixture to a suitable centrifuge tube,and centrifuge at about 2900rpm for about 5minutes.Pass through a suitable filter paper containing a small amount of anhydrous sodium sulfate.Evaporate the filtrate to dryness,and dissolve the residue in 0.5mLof chloroform:the IRabsorption spectrum of this solution exhibits maxima only at the same wavelengths as that of a Standard solution prepared by dissolving 50mg of USP Nortriptyline Hydrochloride RSin 0.5mLof chloroform.
B: Afiltered solution in water of the contents of Capsules,equivalent to nortriptyline hydrochloride solution (1in 20),responds to the tests for Chloride á191ñ,when tested as specified for alkaloidal hydrochlorides.
Dissolution á711ñ
Medium: water;500mL.
Apparatus 1: 100rpm.
Time: 30minutes.
Procedure— Determine the amount of C19H21Ndissolved,employing the procedure set forth in the Assay,making any necessary modifications.
Tolerances— Not less than 80%(Q)of the labeled amount of C19H21Nis dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Phosphate buffer— Dissolve 1.63g of monobasic potassium phosphate in 1liter of water,and adjust with 1Npotassium hydroxide to a pHof 6.7.
Mobile phase— Prepare a filtered and degassed mixture of acetonitrile,methanol,and Phosphate buffer(40:43:17).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Nortriptyline Hydrochloride RSin methanol,and dilute quantitatively,and stepwise if necessary,with methanol to obtain a solution having a known concentration of about 0.38mg per mL.
Assay preparation— Weigh,empty,and combine the contents of not less than 20Capsules.Transfer an accurately weighed portion of the powder,equivalent to about 76mg of nortriptyline hydrochloride,to a 200-mLvolumetric flask,and dissolve in about 150mLof methanol.Shake by mechanical means for 15minutes,dilute with methanol to volume,mix,and filter.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 239-nm detector and a 4.6-mm ×25-cm column that contains packing L10.The flow rate is about 2.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the column efficiency is not less than 500theoretical plates,the tailing factor is not more than 3.0,and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10µL)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 nortriptyline (C19H21N)in the portion of Capsules taken by the formula:
in which 263.38and 299.85are the molecular weights of nortriptyline and nortriptyline hydrochloride,respectively;Cis the concentration,in mg per mL,of USP Nortriptyline Hydrochloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 1404
Phone Number:1-301-816-8165