title: Analytical and semi-preparative enantioresolution of (RS)-ketorolac from pharmaceutical formulation and in human plasma by HPLC.
abstract: An efficient, simple, validated, analytical and semi-preparative HPLC method has been developed for direct enantioresolution of (RS)-Ketorolac (Ket) using monochloro-methylated derivatives of cellulose and amylose, i.e. cellulose (tris-3-chloro-4-methylphenylcarbamate) and amylose (tris-5-chloro-2-methylphenylcarbamate) as chiral stationary phases (CSPs) with photo diode array detection at 320 nm. Enantioresolution was carried out in samples of human plasma spiked with (RS)-Ket under normal and reversed-phase elution modes with suitable mobile phase compositions. The effect of nature of alcohols (MeOH, EtOH, PrOH and n-BuOH) and other solvents (MeCN and MeOH) as organic modifiers in the mobile phase was investigated on the separation performance of two CSPs in terms of retention and separation of enantiomers. The best resolution was observed on cellulose-based CSP using EtOH, while using 2-PrOH (15%) and amylose-based CSP obtained the highest retention. Under reversed-phase elution mode the best enantioseparation was observed using 30% MeCN with ammonium formate buffer. The elution order of enantiomers was ascertained by determining specific rotations. The limit of detection and quantitation values were 5 and 15.5 ng/mL for each enantiomer of (RS)-Ket, respectively. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Chemistry, Lovely Professional University, Phagwara (Punjab), 144411, India.
authors.forename: Manohar
authors.initials: M
authors.lastname: Lal
authors.affiliation: Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, 247667, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Bhushan
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D020910:Ketorolac / Q000097:blood / Q000302:isolation & purification*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004364:Pharmaceutical Preparations; D020910:Ketorolac
keywords: (RS)-ketorolac; HPLC; enantioresolution; monochloro-methylated cellulose and amylose CSP; semi-preparative