Clozapine
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5H-Dibenzo[b,e][1,4]diazepine,8-chloro-11-(4-methyl-1-piperazinyl)-.
8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine [5786-21-0].
»Clozapine contains not less than 98.0percent and not more than 102.0percent of C18H19ClN4,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:Infrared Absorption á197Kñ.
B:
The RFvalue of the principal spot observed in the chromatogram of the Test solutioncorresponds to those of the principal spots observed in the chromatograms of the Standard solutions,as obtained in the test for Chromatographic purity.
Loss on drying á731ñ—
Dry it at 105
for 4hours:it loses not more than 0.5%of its weight.
for 4hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Heavy metals,Method IIá231ñ:
0.002%.
Chromatographic purity—
Adsorbent:
0.25-mm layer of chromatographic silica gel mixture.
Test solution—
Dissolve an accurately weighed quantity of Clozapine in chloroform to obtain a solution containing 10.0mg per mL.
Standard solutions—
Dissolve an accurately weighed quantity of USP Clozapine RSin chloroform,and mix to obtain a solution having a known concentration of 0.1mg per mL.Quantitatively dilute portions of this solution with chloroform to obtain the following solutions.
| Standard solution |
Dilution | Concentration (µg of RSper mL) | Percentage (%, for comparison with test specimen) |
| A | 3in 10 | 30 | 0.3 |
| B | 1in 5 | 20 | 0.2 |
| C | 1in 10 | 10 | 0.1 |
| D | 1in 20 | 5 | 0.05 |
Application volume:
20µL.
Developing solvent system:
a mixture of chloroform and methanol (3:1).
Procedure—
Proceed as directed for Thin-Layer Chromatographyunder Chromatography á621ñ.Examine the plate under short-wavelength UVlight,and compare the intensities of any secondary spots observed in the chromatogram of the Test solutionwith those of the principal spots in the chromatograms of the Standard solutions:no spot from the chromatogram of the Test solutionwith an RFvalue of about 0.82,0.67,or 0.10is larger or more intense than that obtained from Standard solution B,Standard solution C,or Standard solution A,respectively;no other secondary spot from the chromatogram of the Test solutionis larger or more intense than the principal spot obtained from Standard solution C(0.1%);and the sum of the intensities of all secondary spots obtained from the Test solutioncorresponds to not more than 0.6%.
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Assay—
Transfer about 115mg of Clozapine,accurately weighed,to a suitable container,dissolve in 70mLof glacial acetic acid,and titrate with 0.1Nperchloric acid VS,determining the endpoint potentiometrically.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 16.34mg of C18H19ClN4.
Auxiliary Information—
Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 527
Pharmacopeial Forum:Volume No.29(3)Page 623
Phone Number:1-301-816-8165