A sensitive and high-throughput LC-MS/MS method for the determination of ibuprofen: Application to a gender-comparative pharmacokinetic study

Abstract

Ibuprofen is a nonsteroidal anti-inflammatory drug first launched in England in 1969, yet its pharmacokinetic profile in healthy Chinese volunteers remains insufficiently characterized. In this study, a sensitive and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of ibuprofen in plasma. Plasma samples were pretreated via one-step protein precipitation with diclofenac sodium as the internal standard (IS). Chromatographic separation was carried out on a Hedera ODS-2 column with gradient elution utilizing methanol and 5 mM ammonium acetate buffer containing 0.2% acetic acid at a flow rate of 0.35 mL min −1 . LC-MS/MS equipped with an electrospray ionization (ESI) source was used in negative ion mode and multiple-reaction monitoring (MRM) mode with transitions monitored at m/z 205.1→161.1 for ibuprofen and m/z 294.1→250.1 for IS, respectively. Standard curve for ibuprofen was linear from 0.015 to 30 μg mL −1 , illustrating a lower limit of quantitation (LLOQ) than previously reported methods. The intra- and inter-day precision for ibuprofen was below 12.0%, with accuracies within ±7.5%. Extraction recoveries ranged from 84.8 to 91.1%, and matrix effects were between 92.4 and 95.2%. Ibuprofen demonstrated satisfactory stability under various storage conditions. This method was then successfully executed to investigate the pharmacokinetics of ibuprofen after oral administration of ibuprofen sustained-release capsules. Furthermore, the gender effect on the pharmacokinetics of ibuprofen was also evaluated.