Clomipramine Hydrochloride
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C19H23ClN2·HCl 351.31
5H-Dibenz[b,f]azepine-5-propanamine,3-chloro-10,11-dihydro-N,N-dimethyl-,monohydrochloride.
3-Chloro-5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine monohydrochloride [17321-77-6].
»Clomipramine Hydrochloride contains not less than 98.0percent and not more than 102.0percent of C19H23ClN2·HCl,calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
Identification—
A: Infrared Absorption á197Kñ.
B: Ultraviolet Absorption á197Uñ—
Solution: 100µg per mL.
Medium: 0.1Nhydrochloric acid.
Absorptivities at the wavelength of maximum absorbance,calculated on the dried basis,do not differ by more than 1.0%.
pHá791ñ: between 3.5and 5.0,in a solution having a concentration of about 100mg per mL.
Loss on drying á731ñ— Dry it at 105for 2hours:it loses not more than 1.0%of its weight.
Residue on ignition á281ñ: not more than 0.1%.
Chromatographic purity—
TEST1—
Sodium 1-heptanesulfonate solution,System suitability solution,andChromatographic system— Proceed as directed in the Assay.
Mobile phase— Transfer 20.0mLof Sodium 1-heptanesulfonate solution,2.0mLof triethylamine,and 500mLof water to a suitable container,mix,adjust with phosphoric acid to a pHof 3.2±0.1,and dilute with water to 625mL.Transfer to a 1-liter volumetric flask,dilute with acetonitrile to volume,mix,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Test solution— Transfer about 100mg of Clomipramine Hydrochloride,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.
Procedure— Inject a volume (about 5µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure all of the peak responses.Calculate the percentage of each impurity in the portion of Clomipramine Hydrochloride taken by the formula:
100(ri/rs),
in which riis the peak response for each impurity;and rsis the sum of the responses of all the peaks.
TEST2—
Sodium 1-heptanesulfonate solution,Mobile phase,System suitability solution,and Chromatographic system— Proceed as directed in the Assay.
Test solution— Prepare as directed for Test 1.
Procedure— Inject a volume (about 10µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure all of the peak responses.Calculate the percentage of each impurity in the portion of Clomipramine Hydrochloride taken by the formula:
100(ri/rs),
in which riis the peak response for each impurity;and rsis the sum of the responses of all the peaks.Not more than 0.5%of any individual impurity is found;and not more than 2.0%of total impurities is found,the results for Test 1and Test 2being considered.
Assay—
Sodium 1-heptanesulfonate solution— Transfer about 5.5g of sodium 1-heptanesulfonate,accurately weighed,to a 100-mLvolumetric flask,dissolve in 50.0mLof water,and dilute with glacial acetic acid to volume.
Mobile phase— Transfer 20.0mLof Sodium 1-heptanesulfonate solutionand 2.0mLof triethylamine to a 500-mLvolumetric flask,and dilute with water to volume.Transfer this solution to a 1-Lvolumetric flask,adjust with phosphoric acid to a pHof 3.2±0.1,dilute with acetonitrile to volume,mix,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
System suitability solution— Transfer about 7.0mg of USP Desipramine Hydrochloride RSand 10.0mg of USP Imipramine Hydrochloride RS,both accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.
Standard preparation— Dissolve an accurately weighed quantity of USP Clomipramine Hydrochloride RSin methanol,and dilute quantitatively,and stepwise if necessary,with methanol to obtain a solution having a known concentration of about 0.8mg per mL.Transfer 10.0mLof this solution to a 25-mLvolumetric flask,dilute with methanol to volume,and mix.
Assay preparation— Transfer about 80mg of Clomipramine Hydrochloride,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.Transfer 10.0mLof this solution to a 25-mLvolumetric flask,dilute with methanol to volume,and mix.
Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.0mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.85for desipramine and 1.0for imipramine;the resolution,R,between desipramine and imipramine is not less than 0.5;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 C19H23ClN2·HCl in the portion of Clomipramine Hydrochloride taken by the formula:
250C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Clomipramine 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 509
Pharmacopeial Forum:Volume No.27(3)Page 2529
Phone Number:1-301-816-8165