title: Ionic liquid-based dispersive liquid-liquid microextraction followed by RP-HPLC determination of saquinavir in rat serum: application to pharmacokinetics.
abstract: An ionic liquid-based dispersive liquid-liquid microextraction followed by RP-HPLC determination of the most commonly prescribed protease inhibitor, saquinavir, in rat plasma was developed and validated. The effects of different ionic liquids, dispersive solvents, extractant/disperser ratio and salt concentration on sample recovery and enrichment were studied. Among the ionic liquids investigated, 1-butyl-3-methylimidazolium hexafluorophosphate was found to be most effective for extraction of saquinavir from rat serum. The recovery was found to be 95% at an extractant/disperser ratio of 0.43 using 1-butyl-3-methylimidazolium hexafluorophosphate and methanol as extraction and dispersive solvents. The recovery was further enhanced to 99.5% by addition of 5.0% NaCl. A threefold enhancement in detection and quantification limits was achieved, at 0.01 and 0.03 µg/mL, compared with the conventional protein precipitation method. A linear relationship was observed in the range of 0.035-10.0 µg/mL with a correlation coefficient (r(2) ) of 0.9996. The method was validated and applied to study pharmacokinetics of saquinavir in rat serum.
authors.affiliation: Analytical Chemistry Division, Discovery Laboratory D215, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 607, India.
authors.forename: Nageswara Rao
authors.initials: NR
authors.lastname: Ramisetti
authors.forename: Narendra Varma
authors.initials: NV
authors.lastname: Nimmu
authors.forename: Gangu Naidu
authors.initials: GN
authors.lastname: Challa
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D007093:Imidazoles / Q000737:chemistry; D052578:Ionic Liquids / Q000737:chemistry; D057230:Limit of Detection; D016014:Linear Models; D059627:Liquid Phase Microextraction / Q000379:methods*; D008297:Male; D000432:Methanol / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D019258:Saquinavir / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics; D012965:Sodium Chloride
chemical_list: C412621:1-butyl-3-methylimidazolium hexafluorophosphate; D007093:Imidazoles; D052578:Ionic Liquids; D012965:Sodium Chloride; D019258:Saquinavir; D000432:Methanol
keywords: RP-HPLC; dispersive liquid-liquid microextraction; ionic liquid; rat serum; saquinavir