Nortriptyline Hydrochloride Oral Solution

» Nortriptyline Hydrochloride Oral Solution contains nortriptyline hydrochloride equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of nortriptyline (C19H21N).

Packaging and storage— Preserve in tight, light-resistant containers.

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USP Nortriptyline Hydrochloride RS

Identification—

A: Transfer a measured volume of Oral Solution, equivalent to about 50 mg of nortriptyline hydrochloride, to a suitable separator, and render the solution distinctly alkaline (to a pH of 11 or above as indicated by pH indicator paper) by the dropwise addition of 1 N sodium hydroxide. Extract with 15 mL of chloroform, and filter the chloroform extract through about 2 g of anhydrous sodium sulfate that has been previously washed with chloroform. Evaporate the chloroform extract with the aid of heat and a current of air to dryness, and dissolve the residue in 0.5 mL of chloroform: the IR absorption spectrum of this solution exhibits maxima only at the same wavelengths as that of a Standard solution obtained by dissolving 50 mg of USP Nortriptyline Hydrochloride RS in 25 mL of water and proceeding as directed for the test specimen.

B: It responds to the tests for Chloride

191

, when tested as specified for alkaloidal hydrochlorides.

Uniformity of dosage units

905

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for oral solution packaged in single-unit containers: meets the requirements.

Deliverable volume

698

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for oral solution packaged in multiple-unit containers: meets the requirements.

791

: between 2.5 and 4.0.

Alcohol content, Method II

611

: between 3.0% and 5.0% of C2H5OH.

Assay— Transfer an accurately measured volume of Oral Solution, equivalent to about 10 mg of nortriptyline, to a 125-mL separator. Add 20 mL of water, mix, and render the solution distinctly alkaline (to a pH of 11 or above as indicated by pH indicator paper) by the dropwise addition of sodium hydroxide solution (1 in 2). Extract the nortriptyline with four 25-mL portions of chloroform, filtering each extract into a 250-mL beaker through about 12 g of anhydrous sodium sulfate previously washed with 25 mL of chloroform. Rinse the sodium sulfate with four 5-mL portions of chloroform, and collect the rinsings in the beaker. Evaporate the combined chloroform solution with the aid of heat and a current of air to about 10 mL. Transfer the contents of the beaker with the aid of chloroform to a 200-mL volumetric flask. Evaporate the chloroform with the aid of air alone to dryness. [Caution—Do not use heat. ] Dissolve the residue in 1.7 mL of hydrochloric acid, dilute with water to volume, and mix. Transfer 10.0 mL of the solution to a 50-mL volumetric flask, dilute with water to volume, and mix to obtain the Assay preparation. Concomitantly determine the absorbances of the Assay preparation and a Standard solution of USP Nortriptyline Hydrochloride RS in water having a known concentration of about 11.4 µg per mL in 1-cm cells at the wavelength of maximum absorbance at about 239 nm, with a suitable spectrophotometer, using water as the blank. Calculate the quantity, in mg, of C19H21N in the portion of Oral Solution taken by the formula:

(263.38/299.84)(C)(AU / AS)

in which 263.38 and 299.84 are the molecular weights of nortriptyline and nortriptyline hydrochloride, respectively; C is the concentration, in µg per mL, of USP Nortriptyline Hydrochloride RS in the Standard solution; and AU and AS are the absorbances of the Assay preparation and the Standard solution, respectively.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Hariram Ramanathan, M.S. Associate Scientific Liaison 1-301-816-8313	(SM42010) Monographs - Small Molecules 4
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org

USP35–NF30 Page 4089

Pharmacopeial Forum: Volume No. 29(6) Page 1939