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EN
Bicalutamide (BCL) has been approved for treatment of advanced prostate cancer (Pca), and vitamin D is inevitably used in combination with BCL in Pca patients for skeletal or anti-tumor strategies. Therefore, it is necessary to study the effect of vitamin D application on the pharmacokinetics of BCL. We developed and validated a specific, sensitive and rapid UHPLC–MS/MS method to investigate the pharmacokinetic behaviours of BCL in rat plasma with and without the combined use of vitamin D. Plasma samples were extracted by protein precipitation with ether/dichloromethane (2:1 v/v), and the analytes were separated by a Kinetex Biphenyl 100A column (2.1 × 100 mm, 2.6 μm) with a mobile phase composed of 0.5 mM ammonium acetate (PH 6.5) in water (A) and acetonitrile (B) in a ratio of A:B = 35:65 (v/v). Analysis of the ions was run in the multiple reactions monitoring (MRM) mode. The linear range of BCL was 5–2000 ng mL⁻¹. The intra- and inter-day precision were less than 14%, and the accuracy was in the range of 94.4–107.1%. The mean extraction recoveries, matrix effects and stabilities were acceptable for this method. The validated method was successfully applied to evaluate the pharmacokinetic behaviours of BCL in rat plasma. The results demonstrated that the pharmacokinetic property of BCL is significantly affected by combined use of vitamin D, which might help provide useful evidence for the clinical therapy and further pharmacokinetic study.
EN
Galangin (GAL), the major bioactive flavonol extracted from Alpinia officinarum Hance (Zingiberaceae), has attracted much attention due to its multiple biological activities. To develop a fast, reliable, and sensitive ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method for the quantification of GAL in rat plasma and mouse tissues. UHPLC–MS/MS using electrospray ionization operating in negative-ion mode was used to determinate GAL in 18 rats receiving three doses of GAL (2 and 9 mg/kg by intravenous injection, 5 mg/kg by oral administration), with six rats for each dose. Blood samples were collected at 0.0333, 0.25, 0.5, 1, 2, 4, 6 and 8 h. A total of 25 mice received 18 mg/kg GAL by intraperitoneal injection. Liver, heart, lung, spleen, brain, and kidney tissue samples were collected at 0.25, 0.5, 2, 4, and 6 h. The precision of the method was better than 12.1%, while the accuracy ranged from −4.8% to 8.1%. The results of pharmacokinetics demonstrated rapid GAL absorption (tmax of 0.25 h), fast elimination (t1/2 <1.1 h) after three different dosages, and an absolute bioavailability of ~7.6%. Tissue distribution analysis revealed abundant GAL in liver, kidney, spleen, and lung and smaller amounts in brain. The developed method proved fast (3 min), efficient, and reliable, with high selectivity for the quantitative analysis of GAL in biological samples. This is the first study to identify the target tissues of GAL, and the results may help to elucidate the mechanisms underlying its therapeutic effects in vivo.
3
Content available remote A UHPLC–MS/MS method for the quantitation of olmutinib in rat plasma
EN
Olmutinib (Olita™) is an oral third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) which is used to treat non-small cell lung cancer (NSCLC). A simple, rapid, and sensitive method based on ultra-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) has been developed for the determination of olmutinib. Sample preparation was performed following simple one-step protein precipitation with acetonitrile. Olmutinib and internal standard (dasatinib) were separated on an Eclipse Plus C18 RRHD (2.1 × 50 mm, 1.8 μm) column. The mobile phase consisted of acetonitrile–0.1% formic acid in water with gradient elution. A total run time of 1.7 min was achieved. Detection was performed on a positive-ion electrospray ionization mass spectrometer in multiple reaction monitoring (MRM) mode, using transitions of m/z 487.2 → 402.1 for olmutinib and m/z 488.2 → 401 for dasatinib (IS), respectively. The calibration curve (R2 = 0.999) was linear over the range of 1–500 ng/mL. The recovery of olmutinib ranged from 85.8% to 95.5%. This method can be applied to pharmacokinetic studies of olmutinib.
EN
A reliable isotope dilution method for the determination of chloramphenicol (CAP) in drinking water was developed by using an evaporation preparative step. Each sample was monitored by ultrahigh-pressure liquid chromatography (UHPLC) coupled to tandem mass spectrometry (MS/MS) using an electrospray ionization interface (ESI) in negative ion modes. Recoveries of spiked samples were in the range from 93.2% to 95.7% with intra-day relative standard deviation lower than 6.7% and inter-day relative standard deviation lower than 8.2%. Limit of quantification (LOD) was 0.002 ng/mL. The developed method was successfully applied to the analysis of CAP in drinking water of Shannan region of Tibet.
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