Chlordiazepoxide
;)
3H-1,4-Benzodiazepin-2-amine,7-chloro-N-methyl-5-phenyl-,4-oxide.
7-Chloro-2-(methylamino)-5-phenyl-3H-1,4-benzodiazepine 4-oxide [58-25-3].
»Chlordiazepoxide contains not less than 98.0percent and not more than 102.0percent of C16H14ClN3O,calculated on the dried basis.
Packaging and storage—
Preserve in tight,light-resistant containers.
USP Reference standards á11ñ—
USP2-Amino-5-chlorobenzophenone RS.USP Chlordiazepoxide RS.USP Chlordiazepoxide Related Compound A RS.
Identification—
B:
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation as obtained in the Assay.
C:
To about 20mg add 5mLof hydrochloric acid and 10mLof water,and heat to boiling to effect hydrolysis.To the cooled solution add 2mLof sodium nitrite solution (1in 1000),shake,add 1mLof ammonium sulfamate solution (1in 200),then shake for 2minutes,and add 1mLof N-(1-naphthyl)ethylenediamine dihydrochloride solution (1in 1000):a reddish violet color is produced.
Loss on drying á731ñ—
Dry it at 105
for 3hours:it loses not more than 0.3%of its weight.
for 3hours:it loses not more than 0.3%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Heavy metals,Method IIá231ñ:
0.002%.
Related compounds—
Transfer 50.0mg to a 10-mLconical flask,add 2.5mLof acetone,and shake.Allow any undissolved particles to settle,and apply 50µLof the supernatant to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel.Apply to the same plate 10µLof an acetone solution containing 100µg per mLof USP Chlordiazepoxide Related Compound A RSand 10µLof an acetone solution containing 10µg per mLof USP2-Amino-5-chlorbenzophenone RS.Develop the chromatogram in a chromatographic chamber (not previously saturated with the developing solvent)in ethyl acetate 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.Locate the spots on the plate by lightly spraying with 2Nsulfuric acid,drying at 105for 15minutes,and then spraying in succession with sodium nitrite solution (1in 1000),ammonium sulfamate solution (1in 200),and N-(1-naphthyl)ethylenediamine dihydrochloride solution (1in 1000).Any spots from the test solution are not greater in size or intensity than the spots at the respective RFvalues produced by the Standard solutions,corresponding to not more than 0.1%of chlordiazepoxide related compound A,and to not more than 0.01%of 2-amino-5-chlorobenzophenone.
for 15minutes,and then spraying in succession with sodium nitrite solution (1in 1000),ammonium sulfamate solution (1in 200),and N-(1-naphthyl)ethylenediamine dihydrochloride solution (1in 1000).Any spots from the test solution are not greater in size or intensity than the spots at the respective RFvalues produced by the Standard solutions,corresponding to not more than 0.1%of chlordiazepoxide related compound A,and to not more than 0.01%of 2-amino-5-chlorobenzophenone.
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Assay—
[NOTE—Use low-actinic glassware in this procedure.]
Mobile phase—
Prepare a filtered and degassed mixture of methanol and water (60:40).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation—
Dissolve an accurately weighed quantity of USP Chlordiazepoxide RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 200µg per mL.
Assay preparation—
Transfer about 100mg of Chlordiazepoxide,accurately weighed,to a 50-mLvolumetric flask,dissolve in Mobile phase,sonicate for 5minutes,dilute with Mobile phaseto volume,and mix.Pass this solution through a membrane filter having a 0.5-µm or finer porosity.Transfer 10mLof this solution to a 100-mLvolumetric flask,dilute with Mobile phase,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 1mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 3600theoretical plates:the tailing factor is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 5µL)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 C16H14ClN3Oin the portion of Chlordiazepoxide taken by the formula:
0.5C(rU/rS),
in which Cis the concentration,in µg per mL,of the USP Reference Standard in the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Ravi Ravichandran,Ph.D.,Senior Scientist
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 435
Phone Number:1-301-816-8330