title: Enantioselective HPLC resolution of synthetic intermediates of armodafinil and related substances.
abstract: Armodafinil is a unique psychostimulant recently approved by the US Food and Drug Administration for the treatment of narcolepsy. The chromatographic resolution of its chiral intermediates including related substances in the total synthesis of armodafinil was studied on polysaccharide-based stationary phases, viz. cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and amylose tris-(3,5-dimethylphenylcarbamate) (Chiralpak AD-H) by HPLC. The effects of 1-propanol, 2-propanol, ethanol, and trifluoroacetic acid added to the mobile phase and of column temperature on resolution were studied. A good separation was achieved on cellulose-based Chiralcel OD-H column compared to amylose-based Chiralpak AD-H. The effects of structural features of the solutes and solvents on discrimination between the enantiomers were examined. Baseline separation with R(s) >1.38 was obtained using a mobile phase containing n-hexane-ethanol-TFA (75:25:0.15 v/v/v). Detection was carried out at 225 nm with photodiode array detector while identification of enantiomers was accomplished by a polarimetric detector connected in series. The method was found to be suitable not only for process development of armodafinil but also for determination of the enantiomeric purity of bulk drugs and pharmaceuticals.
authors.affiliation: Analytical Chemistry Division, Discovery Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India. rnrao55@yahoo.com
authors.forename: Ramisetti
authors.initials: R
authors.lastname: Nageswara Rao
authors.forename: Dhananjay D
authors.initials: DD
authors.lastname: Shinde
authors.forename: Murali V N
authors.initials: MV
authors.lastname: Kumar Talluri
mesh_terms: D001559:Benzhydryl Compounds / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000077408:Modafinil; D015394:Molecular Structure; D013237:Stereoisomerism; D013696:Temperature; D013816:Thermodynamics
chemical_list: D001559:Benzhydryl Compounds; D000077408:Modafinil