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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]

A sensitive, simple and rapid analytical method based on a liquid chromatography–tandem mass spetrometry (LC–MS/MS) has been established and validated for the determination of stachyose in rat plasma. Plasma samples were prepared by protein precipitation with acetonitrile. Separation of stachyose and nystose (internal standard, IS) was achieved using acetonitrile-water (55:45, v/v) as the mobile phase at a flow rate of 1 ml/min for 6 min on an Asahipak NH 2 P-50 4E column with an Asahipak NH2P-50G 4A guard column. Detection and quantification were conducted by LC–MS/MS method in the negative ion mode using multiple reaction monitoring (MRM) transitions at m / z [M–H] − 665.4 → 383.1 for stachyose and 665.5 → 485.0 for IS, respectively. The method was linear over the concentration ranges of 100–30000 ng/ml with a lower limit of quantification (LLOQ) of 100 ng/ml. The intra- and inter- day precision were all within 8.7% and the accuracy ranged from 97.2–108.4% and 98.3–102.4%, respectively. Stability studies indicated that stachyose was stable under short-term, long-term and three freeze-thaw storage conditions. The method was successfully applied to a pharmacokinetic study involving pulmonary administration of micronized Rehmannia glutinosa oligosaccharides (RGOS) to 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]

A simple and selective specific high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for determination of isobavachalcone (IBC) in rat plasma was developed. Neobavaisoflavone was used as an internal standard (IS). After protein precipitation with acetonitrile (2:1, v/v), the analyte and IS were separated on a 2.6 μm Kinetex C 18 column (100 mm × 2.1 mm i.d., Phenomenex) by isocratic elution with acetonitrile:water (60:40, v/v) as the mobile phase at a flow rate of 0.2 mL/min. An electrospray ionization (ESI) source was applied and operated in the negative ion mode; multiple reactions monitoring (MRM) mode was used for quantification, and the target fragment ions m / z 323.0 → 118.9 for IBC and m / z 321.1 → 265.0 for the IS were chosen. Good linearity was observed in the concentration range of 3.79–484.5 ng/mL for IBC in rat plasma. The recovery of IBC in plasma was in the range of 81.2–89.8%. Intra-day and inter-day precision were both lower than 10%. This method was suitable for pharmacokinetic studies after oral administration of 80 mg/kg IBC in rats. We also obtained pharmacokinetic parameters and concentration–time profiles for IBC after oral administration of IBC in rats. [ABSTRACT FROM AUTHOR]

CAT ((+)-(13aS)-deoxytylophorinine) is a novel anticancer drug belonging to phenanthroindolizidine alkaloids. A sensitive and reliable liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for simultaneous quantification of CAT and its pharmacologically active 3-O-desmethyl metabolite (S-4) was developed and validated in rat plasma using rotundine as the internal standard (IS). CAT, S-4 and IS were extracted by acetonitrile protein precipitation and separated on an Eclipse XDB-C18 column (1.8 μm, 4.6 mm × 50 mm) with acetonitrile–water (27:73, v/v) mobile phase containing 0.1% formic acid at a 0.4 mL/min flow rate. Positive ion electrospray ionization in multiple reaction monitoring mode was employed to measure CAT, S-4 and IS by monitoring the transitions m/z 364.2 → 70.1 for CAT, 350.1 → 70.1 for S-4 and 356.2 → 192.2 for IS. Good linear correlation ( r 2 > 0.991) was achieved for CAT and S-4 over the range of 0.214–128.16 and 0.044–11.00 ng/mL, respectively. The lower limit of quantification was 0.214 ng/mL for CAT and 0.044 ng/mL for S-4, using 50 μL rat plasma samples. The intra- and inter-day precisions were not exceed 15% and the accuracy ranged between 94.80% and 108.22%. The average extraction recoveries of both analytes were greater than 94.62%. The method was successfully applied to the pharmacokinetic study of CAT and S-4 in rats after oral administration. [ABSTRACT FROM AUTHOR]

7-O-Succinyl macrolactin A (SMA) and its major metabolite macrolactin A (MA) are generated from Bacillus polyfermenticus KJS-2. Both substances show inhibitory effects on angiogenesis and cancer cell invasion. SMA in rat plasma is known to be relatively stable at room temperature, but MA was not detected due to its instability. Therefore, a stabilizer is required to accurately measure the substance in biological rat samples. In this study, NaF and eserine were examined to determine whether they could stabilize MA to allow for accurate measurement in rat plasma. We also developed a rapid and simple chromatographic method using tandem mass spectrometry (MS/MS) for the simultaneous determination of these compounds in rat plasma. After simple protein precipitation with acetonitrile including methaqualone (internal standard), the analytes were chromatographed on a Hilic column with a mobile phase of 10 mM formic acid aqueous solution, methanol, and acetonitrile (15:15:70, 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 compounds over time following intravenous administration of a salt form of SMA in rats. [ABSTRACT FROM AUTHOR]

A rapid and sensitive LC-MS/MS method was developed for the quantification of vilazodone in rat plasma using escitalopram as internal standard. After extracted with organic solvent, post-treatment samples were chromatographed on an Agela C18 column. An isocratic mobile phase of acetonitrile: 5 mM ammonium acetate: formic acid (35:65:0.1, v/v/v) was applied at a flow rate of 0.25 mL/min. Detection was performed using multiple reaction-monitoring (MRM) modes at m/z 442.4 → 155.3 for vilazodone and m/z 325.1 → 109.0 for escitalopram. The method was linear in the concentration range of 1.0 - 100 ng/mL with a correlation coefficient ≥0.993. The intra- and inter-assay precision (%RSD) values were within 13.4%, and intra- and inter-day accuracy (%RE) ranged from -9.8 to 6.9%. The total analysis time was 2.2 min. The LC-MS/MS method was fully validated for its sensitivity, selectivity, stability, matrix effect and recovery. The data indicated that the developed method was rapid, specific and sensitive. This method was further and successfully applied in the pharmacokinetics study of vilazodone in rat. [ABSTRACT FROM AUTHOR]

Highlights: [•] The ex vivo stability of bilobalide was investigated for the first time. [•] Effective strategies to stabilize bilobalide in rat blood and plasma were developed. [•] An LC–MS/MS method for determining bilobalide in rat plasma was fully validated. [•] An LOQ of 5.0ng/mL was achieved with consumption of only 20μL of plasma. [ABSTRACT FROM AUTHOR]

Highlights: [•] A LC–MS/MS method was first developed and validated for the determination of deoxypodophyllotoxin in rat plasma. [•] Good peak shape and sensitivity with acceptable matrix effect could be obtained. [•] It is the first pharmacokinetic study of the intravenous administration of DPT in rats. [•] The pharmacokinetic parameters were obtained through two-compartment intravenous models analysis. [ABSTRACT FROM AUTHOR]

Highlights: [•] LC–ESI-MS/MS utilized for PK study of five phenolic components and paeoniflorin in Cerebralcare granule®. [•] The assay simultaneously determines five phenolic components and paeoniflorin in rat plasma. [•] LLOQs of these six active components are below 5.0ng/ml. [•] This is the first pharmacokinetic study of multiple components in Cerebralcare granule®. [ABSTRACT FROM AUTHOR]

Abstract: TM-25659 compound, a novel TAZ modulator, is developed for the control of bone loss and obesity. TAZ is known to bind to a variety of transcription factors to control cell differentiation and organ development. A selective and sensitive method was developed for the determination of TM-25659 concentrations in rat plasma. The drug was measured by liquid chromatography–tandem mass spectrometry after liquid–liquid extraction with ethyl acetate. TM-25659 and the internal standard imipramine were separated on a Hypersil GOLD C18 column with a mixture of acetonitrile–ammonium formate (10mM) (90:10, v/v) as the mobile phase. The ions m/z 501.2→207.2 for TM-25659 and m/z 281.0→86.0 for imipramine in multiple reaction monitoring mode were used for the quantitation. The calibration range was 0.1–100μg/ml with a correlation coefficient greater than 0.99. The lower limit of quantitation of TM-25659 in rat plasma was 0.1μg/ml. The percent recoveries of TM-25659 and imipramine were 98.6% and 95.7% from rat plasma, respectively. The intra- and inter-batch precisions were 3.17–15.95% and the relative error was 0.38–10.82%. The developed assay was successfully applied to a pharmacokinetic study of TM-25659 administered intravenously (10mg/kg) to rats. [Copyright &y& Elsevier]