title: Development and validation of a high performance liquid chromatographic method for the separation of exo and endo isomers of granatamine (9-methyl-9-azabicyclo[3.3.1]nonan-3-amine); a key intermediate of granisetron.
abstract: A simple and accurate high-performance liquid chromatographic method was developed for the determination of exo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine in endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine, commercially known as grantamine and used as a key intermediate in the preparation of granisetron bulk drug. Chromatographic separation of the exo and endo isomers of 9-methyl-9-azabicyclo[3.3.1]nonan-3-amine was achieved on an Inertsil C8 column using a mobile phase containing 0.3% trifluoroacetic acid. The resolution between the two isomers was found to be more than 4. The limit of detection (LOD) and limit of quantification (LOQ) of exo isomer were 0.8 and 2.5 microg x mL(-1) respectively, for a 10 microL injection volume. The percentage recovery of exo-isomer ranged from 99 to 102% w/w in the endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine sample. The test solution and mobile phase were observed to be stable up to 48 h after preparation. The validated method yielded good results for precision, linearity, accuracy, robustness and ruggedness. The proposed method was found to be suitable and accurate for the quantitative determination of exo-isomer in bulk samples of endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine.
authors.affiliation: Analytical Research, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd., Visakhapatnam, India.
authors.forename: S Radha
authors.initials: SR
authors.lastname: Krishna
authors.forename: P Suresh
authors.initials: PS
authors.lastname: Babu
authors.forename: B M
authors.initials: BM
authors.lastname: Rao
authors.forename: N Someswara
authors.initials: NS
authors.lastname: Rao
mesh_terms: D000932:Antiemetics / Q000032:analysis*; D001643:Bridged Bicyclo Compounds / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D017829:Granisetron / Q000032:analysis*; D007202:Indicators and Reagents; D007536:Isomerism; D015203:Reproducibility of Results; D012996:Solutions
chemical_list: D000932:Antiemetics; D001643:Bridged Bicyclo Compounds; D017829:Granisetron; D007202:Indicators and Reagents; D012996:Solutions; C547426:9-methyl-9-azabicyclo(3.3.1)nonan-3-amine