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Amitriptyline Hydrochloride
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C20H23N·HCl 313.86

1-Propanamine, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-, hydrochloride.
10,11-Dihydro-N,N-dimethyl-5H-dibenzo[a,d]cycloheptene-D5,-propylamine hydrochloride [549-18-8].
» Amitriptyline Hydrochloride contains not less than 99.0 percent and not more than 100.5 percent of C20H23N·HCl, calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
Identification—
B: Ultraviolet Absorption 197U—
Solution: 10 µg per mL.
Medium: methanol.
Absorptivities at 239 nm, calculated on the dried basis, do not differ by more than 3.0%.
C: It responds to the tests for Chloride 191.
Melting range 741: between 195 and 199.
pH 791: between 5.0 and 6.0, in a solution (1 in 100).
Loss on drying 731— Dry it at a pressure not exceeding 5 mm of mercury at 60 to constant weight: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Chromatographic purity—
Standard solutions— Dissolve USP Amitriptyline Hydrochloride RS in methanol, and mix to obtain a solution having a known concentration of 0.8 mg per mL. Quantitatively dilute this solution with methanol to obtain Standard solutions, designated below by letter, having the following compositions:
Standard
Preparation		 Dilution Concentration
(µg RS
per mL)		 Percentage
(%, for
comparison
with test
specimen)
A (1 in 2) 400 1.0
B (1 in 4) 200 0.5
C (1 in 5) 160 0.4
D (1 in 10) 80 0.2
E (1 in 20) 40 0.1
Test solution— Dissolve an accurately weighed quantity of Amitriptyline Hydrochloride in methanol to obtain a solution containing 40 mg per mL.
Procedure— Apply separately 10 µL of the Test solution and 10 µL of each Standard solution to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the applications to dry, position the plate in a chromatographic chamber, and develop the chromatograms in a solvent system consisting of a mixture of chloroform, methanol, and ammonium hydroxide (135:15:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow the solvent to evaporate. Examine the plate under short-wavelength UV light. Compare the intensities of any secondary spots observed in the chromatogram of the Test solution with those of the principal spots in the chromatograms of the Standard solutions. [NOTE—Disregard any spots observed at the origins of the chromatograms.] No secondary spot from the chromatogram of the Test solution is larger or more intense than the principal spot obtained from Standard solution B (0.5%), and the sum of the intensities of all secondary spots obtained from the Test solution corresponds to not more than 1.0%. Disregard any spot in the chromatogram of the Test solution that is smaller or less intense than the principal spot obtained from Standard solution E (0.1%).
Organic volatile impurities, Method I 467: meets the requirements.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 1 g of Amitriptyline Hydrochloride, accurately weighed, in 30 mL of glacial acetic acid, warming slightly if necessary to effect solution. Cool, add 10 mL of mercuric acetate TS, then add crystal violet TS, and titrate with 0.1 N perchloric acid VS to a green endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 31.39 mg of C20H23N·HCl.
Auxiliary Information— Staff Liaison : Ravi Ravichandran, Ph.D., Senior Scientist
Expert Committee : (MDPP05) Monograph Development-Psychiatrics and Psychoactives
USP29–NF24 Page 148
Pharmacopeial Forum : Volume No. 29(6) Page 1844
Phone Number : 1-301-816-8330