title: A validated chiral LC method for the enantiomeric separation of Zolmitriptan key intermediate, ZTR-5.
abstract: A new and accurate chiral liquid chromatographic method was described for the enantiomeric separation of ZTR-5 [(4S)-4-(4-aminobenzyl)-2-oxazolidinone, (S)-isomer], a key intermediate of Zolmitriptan in bulk drugs. The enantiomers of ZTR-5 were baseline resolved on a Chiralpak AD-H (250 mm x 4.6 mm, 5 microm) column using a mobile phase system containing hexane:ethanol (70:30, v/v). The resolution between the enantiomers was not less than four and interestingly distomer was eluted prior to eutomer. The limit of detection and limit of quantification of (4R)-4-(4-aminobenzyl)-2-oxazolidinone [(R)-isomer] were found to be 250 and 750 ng/ml, respectively, for 10 microl injection volume. The percentage recovery of (R)-isomer ranged from 92.0 to 105.6 in the bulk drug samples of ZTR-5. The validated method yielded good results regarding precision, linearity, accuracy and ruggedness. The proposed method was found to be suitable and accurate for the quantitative determination of (R)-isomer in bulk drug samples of ZTR-5.
authors.affiliation: Analytical Research, Custom Pharmaceutical Services, Dr. Reddy's Laboratories, Hyderabad 500049, India. srinivasmk@drreddys.com
authors.forename: M K
authors.initials: MK
authors.lastname: Srinivasu
authors.forename: B Mallikarjuna
authors.initials: BM
authors.lastname: Rao
authors.forename: G
authors.initials: G
authors.lastname: Sridhar
authors.forename: K B
authors.initials: KB
authors.lastname: Chandrasekhar
authors.forename: P Rajender
authors.initials: PR
authors.lastname: Kumar
mesh_terms: D000688:Amylose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid / Q000295:instrumentation* / Q000379:methods*; D004345:Drug Industry / Q000379:methods; D007536:Isomerism; D008956:Models, Chemical; D015394:Molecular Structure; D023303:Oxazolidinones / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D048448:Phenylcarbamates / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013237:Stereoisomerism; D013997:Time Factors; D014363:Tryptamines / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D023303:Oxazolidinones; D048448:Phenylcarbamates; D014363:Tryptamines; C506723:ZTR-5 compound; C080033:Chiralpak AD; C089750:zolmitriptan; D000688:Amylose