Analysis of ibuprofen enantiomers in rat plasma by liquid chromatography with tandem mass spectrometry

Abstract

A sensitive and selective method for the analysis of ibuprofen enantiomers by LC-MS/MS was developed and validated for the purpose of application in pharmacokinetic studies in small experimental animals. Aliquots of 200 μL plasma were submitted to liquid-liquid extraction with hexane/diisopropylether (50:50 v/v) in acid pH. Separation was accomplished in a Chirex® 3005 (250 × 4.6 mm, 5 μm) column at 25°C with a mobile phase that consisted of 0.01 M ammonium acetate in methanol at a flow rate of 1.1 mL/min. The mass spectrometer consisted of an ESI interface operating at negative ionization mode and multiple reaction monitoring. The transitions 205 > 161 and 240 > 197 were monitored for ibuprofen enantiomers and fenoprofen (internal standard), respectively. Method validation included the evaluation of the matrix effect, stability, linearity, lower LOQ, within-run and between-run precision, and accuracy. The lower LOQ was 25 ng/mL for each ibuprofen enantiomer, and the calibration curves showed good linearity in the range 0.025-50 μg/mL. The method was successfully applied in the investigation of pharmacokinetic disposition of ibuprofen enantiomers in rats treated orally with 25 mg/kg of the racemate. Enantioselective kinetic disposition was observed with accumulation of (+)-(S)-ibuprofen in rats following single oral administration.

Simultaneous enantioseparation of nonsteroidal anti-inflammatory drugs by a one-dimensional liquid chromatography technique using a dynamically coated chiral porous silicon pillar array column

“…This order of elution has been observed in chiral separation of ibuprofen by β-cyclodextrin based [33,34] other chiral HPLC columns e.g. ((R)-1-naphthylglycine and 3,5-dinitrobenzoic acid amide) [35,36].…”

UPLC–MS method for the simultaneous determination of naproxen, fluvastatin and ibuprofen in waste water samples

“…Normally the technique has shown advantages over other analytical methods since it does not need derivatization of the pollutants for their determination even in trace level [19,20,22]. Other than the industrial waste the drugs has also been determined in biological matrices [23,24]. The distribution and transportation of various drugs which may result as pollutants or may be exposed to the humans through the food chain or through the supplied water demands the analysis of pharmaceuticals in the industrial waste water samples.…”

A Validated Chiral LC–MS/MS Method for the Enantioselective Determination of (S)-(+)- and (R)-(-)-Ibuprofen in Dog Plasma: Its Application to a Pharmacokinetic Study

“…Mass spectrometers are good alternatives for overcoming these limitations owing to their high throughput, sensitivity, and selectivity [ 35 , 36 , 37 ]. Indeed, several previously developed liquid chromatography methods with tandem mass spectrometry detection (LC–MS/MS) are available for the analysis of ibuprofen enantiomers in biological samples [ 38 , 39 , 40 , 41 , 42 , 43 ]. Nevertheless, most of these methods show comparably low sensitivity (limit of detection, 20–50 ng/mL) [ 38 , 41 , 42 ], insufficient recovery [ 38 , 41 , 43 ], and require a large sample volume (100–500 µL of plasma) for analysis [ 39 , 40 , 42 , 43 ].…”