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LNA-i-miR-221, a 13-mer oligonucleotide, is a new miR-221 inhibitor that could be used as a novel drug for multiple myeloma. Herein, an ion-pair reversed phase liquid chromatography–tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the quantification of LNA-i-miR-221 in rat plasma. Plasma samples were prepared with an initial phenol/chloroform/isoamyl alcohol liquid–liquid extraction followed by a solid phase extraction. Chromatographic separation was performed with a gradient system on a HALO C18 column using hexafluoro-2-propanol/triethylamine buffer and methanol as mobile phase at a flow rate of 0.4 mL/min. Under these conditions LNA-i-miR-221 and the analogue internal standard are co-eluted at 1.2 min. The detection was carried out in multiple reaction monitoring (MRM) mode using a negative electrospray ionization (ESI) interface. The assay showed a good linearity within the calibration range 10–10000 ng/mL. The precision, accuracy, and recovery values were found to be <15% (<20% at LLOQ), 100 ± 15%, and 97.6–103.7%, respectively. This method was successfully applied to measure the concentrations of LNA-i-miR-221 in plasma samples following the intravenous administration during a 4-week toxicity study in rats. [ABSTRACT FROM AUTHOR]

3- O -Acetyloleanolic acid (OAA) is a triterpenoid compound, and exerts an apoptosis in cancer cell lines, an inhibition of both atopic and allergic contact dermatitis in murine model, and a suppression of inflammatory bone loss in mice. OAA can be converted into oleanolic acid (OA) by hydrolysis in vivo , and OA exhibits several pharmacological effects as well. A liquid chromatographic method using tandem mass spectrometry (MS/MS) was developed for the simultaneous determination of OAA and OA in rat plasma. After liquid–liquid extraction with ethylacetate, both substances were chromatographed on a reversed phase column with a mobile phase of 0.1% formic acid aqueous solution and acetonitrile (1:9, v/v). The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This analytical method was successfully applied to monitor plasma concentrations of both substances over time following an intravenous administration of OAA in rats. [ABSTRACT FROM AUTHOR]

( E )-Methyl-4-aryl-4-oxabut-2-enoate (YH-8) is a novel PKnB protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography–tandem mass spectrometric (LC--MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid--liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol--water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring (SRM) mode. Method validation revealed good linearity over the range of 1–500 ng/mL for YH-8 with a lower limit of quantification (LLOQ) of 1 ng/mL. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%–6.8%, with accuracy of the method being 100.69%–106.18%. Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to 15 days at −70 °C, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg. [ABSTRACT FROM AUTHOR]

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 × 2 mm, 5 μm) at ambient temperature using isocratic elution with acetonitrile-water (45:55, v/v) containing 5 mM ammonium formate buffer (finally adjusted to apparent pH* = 5.0 with formic acid) at a flow rate of 0.4 mL/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 0.5–1000 ng/mL with the lower limit of quantification (LLOQ) of 0.5 ng/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. [ABSTRACT FROM AUTHOR]

A simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the quantification of milnacipran (MC) in rat plasma by using the liquid–liquid extraction method. Milnacipran-d10 (MCD10) was used as an internal standard (IS). Chromatographic separation was achieved on Zorbax SB-CN (4.6mm×75mm, 3.5µm) column with an isocratic mobile phase composed of 10mM ammonium acetate (pH 4.0) and methanol in the ratio of 25:75(v/v), at a flow-rate of 0.7mL/min. MC and MCD10 were detected with proton adducts at m/z 247.2→230.3 and m/z 257.2→240.4 in multiple reaction monitoring (MRM) positive mode respectively. The method was validated over a linear concentration range of 1.00–400.00ng/mL with a correlation coefficient (r 2)≥0.9850. This method demonstrated intra- and inter-day precision within 5.40–10.85% and 4.40–8.29% and accuracy within 97.00–104.20% and 101.64–106.23%. MC was found to be stable throughout three freeze–thaw cycles, bench top and postoperative stability studies. This method was successfully applied to a pharmacokinetic study of rats through i.v. administration. [ABSTRACT FROM AUTHOR]