Determination of ibuprofen enantiomers in human plasma by LC-MS/MS in pharmacokinetics study
10.16438/j.0513-4870.2017-0213
- VernacularTitle:LC-MS/MS法测定人血浆中布洛芬对映体浓度及其药动学研究
- Author:
Ming HUANG
1
;
Quan-ying ZHANG
1
;
Shun-lin ZONG
1
Author Information
1. Clinical Pharmacology Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
ibuprofen;
chiral enantiomer;
LC-MS/MS;
pharmacokinetics
- From:
Acta Pharmaceutica Sinica
2017;52(10):1587-1591
- CountryChina
- Language:Chinese
-
Abstract:
The study aims to establish an LC-MS/MS method for the determination of S-(+)-ibuprofen (S-IBP) and R-(-)-ibuprofen (R-IBP), which may be used subsequently to investigate the pharmacokinetics of ibuprofen enantiomers in healthy Chinese volunteers. Naproxen was used as an internal standard. The separation was achieved on a Chiralpak AD-3R column (4.6 mm×150 mm, 3.0 μm) with a mobile phase consisting of acetonitrile/0.01% formic acid aqueous solution (40:60) at a flow rate of 750 μL·min-1 within 23.0 min. Naproxen and the internal standard were measured by a triple-quadrupole mass spectrometer in negative electron electronic spray ion (ESI) mode using multiple reaction monitoring (MRM). The extracted ions monitored following MRM transitions were m/z 205.1→161.0 for ibuprofen enantiomers and m/z 229.1→185.0 for the internal standard naproxen. Plasma samples were pretreated through methanol precipitation. The calibration curve of S-IBP and R-IBP in human plasma was linear over the concentration rang of (0.05-30.00) μg·mL-1. The lower limit of quantitation was 0.05 μg·mL-1. The intra-and inter-run precisions of S-IBP at three quality control levels were within 2.2%-4.2%, the relative deviation of the assay was within -12.0%-13.0%. The intra-and inter-run precisions of R-IBP at three quality control levels were within 2.0%-8.2%, the relative deviation of the assay was within -11.5%-10.6%. The plasma samples were stable at room temperature (25℃) for 6 h, at -30℃ for 47 days and during three freeze-thaw cycles. The method was proved to be convenient, accurate and sensitive, and suitable for the pharmacokinetics study of ibuprofen enantiomers in healthy Chinese volunteers after a single oral dose of 300 mg ibuprofen extended-release capsule.
