Nortriptyline Hydrochloride Oral Solution

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Nortriptyline Hydrochloride Oral Solution contains nortriptyline hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of nortriptyline (C₁₉H₂₁N).

2 IDENTIFICATION

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A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197S _{(USP 1-May-2021)}

Standard solution: Dissolve 50 mg of USP Nortriptyline Hydrochloride RS in 25 mL of water and transfer to a suitable separatory funnel. Adjust by the dropwise addition of 1 N sodium hydroxide to a pH of NLT 11. The pH can be checked with pH indicator paper. 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. Dissolve the residue in 0.5 mL of chloroform.

Sample solution: Transfer a suitable volume of Oral Solution containing about 50 mg of nortriptyline hydrochloride to a suitable separatory funnel. Adjust by the dropwise addition of 1 N sodium hydroxide to a pH of NLT 11. The pH can be checked with pH indicator paper. 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. Dissolve the residue in 0.5 mL of chloroform.

Acceptance criteria: The IR absorption spectrum of the Sample solution exhibits maxima only at the same wavelengths as those of the Standard solution.

Change to read:

B. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests, Chloride: Meets the requirements of the test for amine hydrochlorides_{(USP 1-May-2021)}

3 ASSAY

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PROCEDURE

Standard solution: 11.4 µg/mL of USP Nortriptyline Hydrochloride RS in water

Sample solution: Nominally 10 µg/mL of nortriptyline prepared as follows. Transfer a measured volume of Oral Solution equivalent to 10 mg of nortriptyline to a suitable separatory funnel. Add 20 mL of water and mix. Adjust by the dropwise addition of 50% sodium hydroxide TS to a pH of NLT 11. The pH can be checked with pH indicator paper. Extract the nortriptyline with four 25-mL portions of chloroform, filtering each extract into a suitable beaker through 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, and dilute with water to volume. Transfer 10.0 mL of the solution to a 50-mL volumetric flask, and dilute with water to volume.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).) _{(USP 1-May-2021)}

Mode: UV

Analytical wavelength: About 239 nm

Cell: 1 cm

Blank: Water

Analysis

Samples: Standard solution, Sample solution, and Blank

Calculate the percentage of the labeled amount of nortriptyline (C₁₉H₂₁N) in the portion of Oral Solution taken:

Result = (A_u /A_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Nortriptyline Hydrochloride RS in the Standard solution (µg/mL)

C_u = nominal concentration of nortriptyline in the Sample solution (µg/mL)

M_r1 = molecular weight of nortriptyline, 263.38

M_r2 = molecular weight of nortriptyline hydrochloride, 299.84

Acceptance criteria: 90.0%–110.0%

4 OTHER COMPONENTS

ALCOHOL DETERMINATION (611), Procedures. Method II: 3.0%-5.0% of Ethanol (C₂H₅OH)

5 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905)

For Oral Solution packaged in single-unit containers: Meets the requirements

DELIVERABLE VOLUME (698)

For Oral Solution packaged in multiple-unit containers: Meets the requirements

6 SPECIFIC TESTS

PH (791): 2.5-4.0

7 ADDITIONAL REQUIREMENTS

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PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature _{(USP 1-May-2021)}

USP REFERENCE STANDARDS (11)

USP Nortriptyline Hydrochloride RS