Development and validation of an LC-MS/MS method for the determination of a novel thienoquinolin urea transporter inhibitor PU-48 in rat plasma and its application to a pharmacokinetic study.

A specific, sensitive and stable high-performance liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative determination of methyl 3-amino-6-methoxythieno [2,3-b]quinoline-2-carboxylate (PU-48), a novel diuretic thienoquinolin urea transporter inhibitor in rat plasma. In this method, the chromatographic separation of PU-48 was achieved with a reversed-phase C18 column (100 × 2.1 mm, 3 μm) at 35°C. The mobile phase consisted of acetonitrile and water with 0.05% formic acid added with a gradient elution at flow rate of 0.3 mL/min. Samples were detected with the triple-quadrupole tandem mass spectrometer with multiple reaction monitoring mode via electrospray ionization source in positive mode. The retention time were 6.2 min for PU-48 and 7.2 min for megestrol acetate (internal standard, IS). The monitored ion transitions were mass-to-charge ratio (m/z) 289.1 → 229.2 for PU-48 and m/z 385.3 → 267.1 for the internal standard. The calibration curve for PU-48 was linear over the concentration range of 0.1-1000 ng/mL (r2 > 0.99), and the lower limit of quantitation was 0.1 ng/mL. The precision, accuracy and stability of the method were validated adequately. The developed and validated method was successfully applied to the pharmacokinetic study of PU-48 in rats.

Zhang ZY ，Wang X ，Liu D ，Zhang H ，Zhang Q ，Lu YY ，Li P ，Lou YQ ，Yang BX ，Lu C ，Lou YX ，Zhang GL ... -  《-》

Development and validation of a high-throughput method for the quantitative analysis of D-amphetamine in rat blood using liquid chromatography/MS3 on a hybrid triple quadrupole-linear ion trap mass spectrometer and its application to a pharmacokinetic stu

Cesari N ，Fontana S ，Montanari D ，Braggio S ... -  《-》

Development and validation of a rapid high-performance liquid chromatography-tandem mass spectrometry method for the determination of WJ-38, a novel aldose reductase inhibitor, in rat plasma and its application to a pharmacokinetic study.

WJ-38 is an aldose reductase inhibitor that is being developed for the treatment of diabetic complications. The present paper describes a sensitive and specific liquid chromatography-tandem mass spectrometry method for the determination of WJ-38 in rat plasma. Partial denaturation of plasma proteins with methanol followed by liquid-liquid extraction using ethyl acetate was used to extract strongly protein-bound WJ-38 from rat plasma. Chromatographic separation was performed on an Inertsil ODS-3 column with an isocratic mobile phase consisting of acetonitrile, water and formic acid (75:25:0.125, v/v/v). Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an ESI interface operating in positive ionization mode. Quantitation was performed using selected reaction monitoring of precursor-product ion transitions at m/z 392→246 for WJ-38 and m/z 446→321 for glipizide (internal standard). A linear calibration curve was obtained over the concentration range of 10.0-10,000 ng/mL for WJ-38 in rat plasma. The intra- and inter-day precisions were less than 13.6% and the accuracy was within ± 5.3%. The extraction recovery of WJ-38 from rat plasma was over 66.0%. The validated method has been successfully applied to a pharmacokinetic study in rats after intragastrical administration of WJ-38.

Lu J ，Liu Y ，Wang X ，Wang S ，Di X ... -  《-》

An LC-MS/MS method for the quantitation of cabozantinib in rat plasma: application to a pharmacokinetic study.

A simple, rapid and sensitive high-performance liquid chromatography tandem mass-spectrometric method (LC-MS/MS) for the novel multiple tyrosine kinase inhibitor (TKI) cabozantinib was developed and validated using erlotinib as internal standard (IS). Plasma samples were pre-treated by liquid-liquid extraction with ethyl acetate. Separation was achieved on a reversed phase C18 column (50×2mm, 5μm) at ambient temperature using isocratic elution with acetonitrile-water (45:55, v/v) containing 5mM ammonium formate buffer (finally adjusted to apparent pH*=5.0 with formic acid) at a flow rate of 0.4mL/min. The analytes were monitored by a triple quadrupole tandem mass spectrometer with electrospray ionization source in the positive ion mode. Calibration curve was linear (r>0.99) in a concentration range of 0.5-1000ng/mL with the lower limit of quantification (LLOQ) of 0.5ng/mL. Intra- and inter-day accuracy and precision were validated by relative error values (RE) and relative standard deviation values (RSD), respectively, which were both lower than the limit of 15%. This method was successfully applied to a pharmacokinetic study of cabozantinib in rats.

Su Q ，Li J ，Ji X ，Li J ，Zhou T ，Lu W ，Li L ... -  《-》

Development and validation of an LC-MS/MS method for the determination of DPHB in rat plasma and its application in pharmacokinetic studies.

The aim of the present study was to develop a rapid, specific and sensitive LC-MS/MS method for the determination of DPHB [7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-4-hepten-3-one] in rat plasma using yakuchinone A as an internal standard (IS). n-Hexane was used for the extraction of DPHB from rat plasma. Chromatographic separation of DPHB was achieved using a Kinetex XB-C18 column (2.10 × 50 mm, 2.6 μm) at 40°C. The mobile phase consisted of water (containing 0.1‰ formic acid, A) and acetonitrile (containing 0.1‰ formic acid, B) under a gradient elution at a flow rate of 0.3 mL min-1 . Positive electrospray ionization and multiple reaction monitoring mode were used for detection. The selected precursor ion to product ion pairs, m/z 311.3 → 137.0 for DPHB and m/z 313.1 → 137.0 for yakuchinone A, were monitored. Good linearity was observed over the concentration range from 2 to 2000 ng mL-1 (r = 0.9969). The recovery efficiency of DPHB from rat plasma was 54.8-69.7%, while the matrix effect ranged from 99.7 to 113%. Intra- and inter-day precision and accuracy values were within ±15% at three different quality control concentration levels. This validated method was successfully applied to pharmacokinetic studies in rats after a single p.o. or i.v. dose of DPHB solution. The route of administration significantly influenced systemic exposure to DPHB, and low bioavailability of DPHB was observed. The method developed here will be further improved and used in future pharmacokinetic studies.

Wen Q ，Li HL ，Chen F ，Gong JW ，Guan WW ，Fu NG ，Tan YF ... -  《-》