Isomer Ratio in Clomiphene Citrate

DETERMINATION OF CIS-TRANS ISOMER RATIO IN CLOMIPHENE CITRATE 

Theory It is an established fact that cis- and /raws-substituted double bonds have slightly different absorption bands in the region of 13 pm. This specific feature forms the basis of the present determination. 

Besides, the pharmacological actions of many compounds are invariably dependent on the shape of molecules and hence, usually play a very significant role. Therefore, if both cis- and tram-isomers are produced in the course of a particular synthesis it may be absolutely necessary to incorporate in the product profile a specific test for the relative proportions of one to the other. This type of control measure strictly conforms the uniformity of composition in the bulk-drug industry and ensures a check on the batch-to-batch variation. 

Procedure Dissolve accurately 22.5 mg of /ram-clomiphene citrate and 52.5 mg of cis-clomiphene citrate (approx. 1 2.3) into 10 ml of DW in a clean 50 ml separating funnel. Add to it 1 ml solution of sodium hydroxide (5% w/v in DW). In the alkaline medium the base is liberated which is extracted successively with 3 portions of solvent ether (10 ml each). The combined ethereal layer is washed with two portions of DW (10 ml each). The resulting ethereal fraction is dried over anhydrous sodium sulphate, filter, evaporate to diyness carefully over an electric water-bath and dissolve the residue in 1 ml of CS2. Now, record the absorption curve in a 0.2 mm cell over the range 12.50 to 14.00 pm. Calculate the absorbance for the peaks at 13.16 and 13.51 pm respectively by employing the base-line method (see section 3. l. B in this chapter) between the minima at 12.66 and 13.89 pm. 

Finally, repeat the assay with a 1 1 mixture (75 mg) of cis and /raws-clomiphene citrates and also with clomiphene citrate (75 mg) as such. Thus, calculate the ratio as follows  

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Determination of cis-trans isomer ratio in clomiphene citrate... 

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