Development and validation of sensitive methods for determination of sibutramine hydrochloride monohydrate and direct enantiomeric separation on a protein-based chiral stationary phase.
Sibutramine hydrochloride monohydrate, chemically 1-(4-chlorophenyl)-N,N-dimethyl-alpha-(2-methylpropyl) hydrochloride monohydrate (SB.HCI.H20), was approved by the U.S. Food and Drug Administration for the treatment of obesity. The objective of this study was to develop, validate, and compare methods using UV-derivative spectrophotometry (UVDS) and reversed-phase high-performance liquid chromatography (HPLC) for the determination of SB.HCI.H20 in pharmaceutical drug products. The UVDS and HPLC methods were found to be rapid, precise, and accurate. Statistically, there was no significant difference between the proposed UVDS and HPLC methods. The enantiomeric separation of SB was obtained on an alpha-1-acid glycoprotein column. The R- and S-sibutramine were eluted in < 5 min with baseline separation of the chromatographic peaks (alpha = 1.9 and resolution = 1.9).
Universidade de São Paulo, Faculdade de Ciências Farmacêuticas, Departamento de Farmácia, CP 66355, CEP: 05315-970, São Paulo-SP, Brazil. anil@usp.br
Anil Kumar
AK
Singh
López García
LG
Pedro
Fábio Pereira
FP
Gomes
Helena Miyoco
HM
Yano
Mariangela Tirico
MT
Auricchio
Erika Rosa Maria
ER
Kedor-Hackmann
Maria Inês Rocha Miritello
MI
Santoro
D001067:Appetite Depressants / Q000032:analysis / Q000737:chemistry / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D003503:Cyclobutanes / Q000032:analysis* / Q000737:chemistry / Q000592:standards; D006801:Humans; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D013237:Stereoisomerism
D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine