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LE300 is a novel dopamine receptor antagonist used to treat cocaine addiction. In the current study, a sensitive and fast liquid chromatography–tandem mass spectrometry (LC-MS/MS) has been established and validated for the simultaneous analysis of LE300 and its N-methyl metabolite, MLE300, in rat plasma with an application in a pharmacokinetic study. The chromatographic elution of LE300, MLE300, and Ponatinib (IS, internal standard), was carried out on a 50 mm C18 analytical column (ID: 2.1 mm and particle size: 1.8 μm) maintained at 22 ± 2 °C. The run time was 5 min at a flow rate of 0.3 mL/min. The mobile phase consisted of 42% aqueous solvent (10 mM ammonium formate, pH: 4.2 with formic acid) and 58% organic solvent (acetonitrile). Plasma samples were pretreated using protein precipitation with acetonitrile. The electrospray ionization (ESI) source was used to generate an ion-utilizing positive mode. A multiple reaction monitoring mass analyzer mode was utilized for the quantification of analytes. The linearity of the calibration curves in rat plasma ranged from 1 to 200 ng/mL (r2 = 0.9997) and from 2 to 200 ng/mL (r2 = 0.9984) for LE300 and MLE300, respectively. The lower limits of detection (LLOD) were 0.3 ng/mL and 0.7 ng/mL in rat plasma for LE300 and MLE300, respectively. Accuracy (RE%) ranged from −1.71% to −0.07% and −4.18% to −1.48% (inter-day), and from −3.3% to −1.47% and −4.89% to −2.15% (intra-day) for LE300 and MLE300, respectively. The precision (RSD%) was less than 2.43% and 1.77% for the inter-day, and 2.77% and 1.73% for intra-day of LE300 and MLE300, respectively. These results are in agreement with FDA guidelines. The developed LC-MS/MS method was applied in a pharmacokinetic study in Wistar rats. Tmax and Cmax were 2 h and 151.12 ± 12.5 ng/mL for LE300, and 3 h and 170.4 ± 23.3 ng/mL for MLE300. [ABSTRACT FROM AUTHOR]

Transcriptional coactivator with PDZ-binding motif (TAZ) is considered an attractive target for osteoporosis, obesity, and muscle regeneration. TM-53, a promising TAZ modulator, was recently introduced, and here, we developed a rapid, precise, and reliable analytical method for TM-53 and characterized its pharmacokinetic properties in rat plasma. The hybrid triple quadrupole/linear ion trap coupled to liquid chromatography method was developed and validated to quantify TM-53. Additionally, TM-53 concentrations in plasma were analyzed, and its pharmacokinetic parameters were calculated by non-compartmental analysis. Multiple reaction monitoring at m / z 569.4 → 207.1 showed the most sensitive signals for TM-53, and the linear scope of the standard curve was between 1.5 ng/mL and 500 ng/mL. The intra- and inter-day precisions of the quality control samples were <15%, and their accuracies were ranged from 86.2% to 111.0%. Furthermore, the matrix effects, extraction recoveries, and process efficiencies of this analytical method for evaluating TM-53 in rat plasma were 99.1%, 99.9%, and 99.1% respectively. In short- and long-term stability studies, TM-53 showed good stability under frozen conditions, but TM-53 hydrolysis in the plasma matrix was observed following storage at room temperature. This analytical method was successfully applied for pharmacokinetic analysis of TM-53 in rat plasma and demonstrated excellent sensitivity, selectivity, precision, and accuracy. These data indicated that this method can be applied for further preclinical studies of TM-53. [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]

A specific, sensitive and rapid liquid chromatography tandem mass spectrometry (LC–MS/MS) method has been developed and validated for simultaneous quantification of doxorubicin and curcumin in rat plasma after intravenous administration. The analytes of doxorubicin and curcumin were extracted with methanol precipitation using glibenclamide as internal standard (IS). The chromatographic separation was performed on a C 18 column with acetonitrile and 0.1% formic acid water as mobile phase and with gradient elution at a flow rate of 0.2 mL/min. Calibration curves were linear over the ranges of 2–8000 ng/mL for doxorubicin and 5–2000 ng/mL for curcumin ( r > 0.99). The lower limit of quantification (LLOQ) was 2 ng/mL for DOX and 5 ng/mL for Cur. Finally, this developed method was successfully applied in the pharmacokinetic study of doxorubicin and curcumin in rats and evaluated the effects of curcumin on the absorption of doxorubicin after intravenous administration. [ABSTRACT FROM AUTHOR]

A simple, rapid and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous determination of six components including apigenin, quercetin, apigenin-7- O -β- d -glucoside, quercetin-3- O -β- d -glucoside, 3′-methoxyluteolin-7- O -β- d -glucoside, and tricin-7- O -β- d -glucopyranoside in rat plasma using formononetin as the internal standard (IS). The plasma samples were pretreated by a one-step liquid–liquid extraction with dichloromethane. The chromatographic separation was carried out on a ZORBAX SB-Aq column with a gradient mobile phase consisting of acetonitrile and 2 mM aqueous ammonium acetate. All analytes and IS were quantitated through electrospray ionization in negative ion multiple reaction monitoring mode. The mass transitions were as follows: m / z 269.1 → 117.2 for apigenin, m / z 301.2 → 151.2 for quercetin, m / z 431.3 → 311.2 for apigenin-7- O -β- d -glucoside, m / z 463.2 → 300.2 for quercetin-3- O -β- d -glucoside, m / z 461.3 → 283.1 for 3′-methoxyluteolin-7- O -β- d -glucoside, m / z 491.3 → 313.1 for tricin-7- O -β- d -glucopyranoside, and m / z 267.2 → 252.2 for IS, respectively. All calibration curves exhibited good linearity with correlation coefficient ( r ) > 0.995. The intra-day and inter-day precisions (RSD) at three QC levels were both less than 14.0% and the accuracies ranged from 89.8% to 113.8%. The extraction recoveries of six compounds ranged from 82.3% to 92.5%. The validated method was successfully applied to pharmacokinetic study of the six components in male rat plasma after oral administration of Paulownia tomentosa flower extract. [ABSTRACT FROM AUTHOR]

A simple, rapid and specific high performance liquid chromatography–electrospray ionization tandem mass spectrometry method was developed for simultaneous determination of dabigatran etexilate (BIBR 1048 MS), the intermediate metabolite (BIBR 1087 SE) and dabigatran (BIBR 953 ZW). In this method, a stacked protein precipitation with methanol was performed in Sirocco 96-well filtration plates to extract analytes using only 50 μL plasma. The analysis was performed on an Ultimate TM XB-C18 (4.6 × 50 mm, 5 μm) column using gradient elution with a mobile phase composed of methanol containing 0.01% formic acid and pure water at a flow rate of 0.3 mL/min. The gradient was set to 90% methanol containing 0.01% formic acid for the first 1.0 min, after which it dropped to 10%, and then was kept at 10% for the next 5 min followed by an additional 1.0 min at the initial composition of 90% methanol containing 0.01% formic acid for equilibration. Detection was performed on a triple-quadrupole mass spectrometer electrospray ionization interface in positive ion mode. Linear calibration curves were obtained over the concentration ranges of 1–500 ng/mL for all analytes. The validated LC–MS/MS method for its selectivity, sensitivity, linearity, precision, accuracy, recovery, matrix effect and stability had been successfully applied to a pharmacokinetic study of analytes in rat plasma following a single oral administration of 15 mg/kg dabigatran etexilate. [ABSTRACT FROM AUTHOR]

Highlights: [•] Method to determine six components in APE and one metabolite of AND was developed. [•] AND was found to be unstable in rat plasma and could be stabilized via acidification. [•] The method was applied successfully in a rat pharmacokinetic study. [ABSTRACT FROM AUTHOR]

Background Yakuchinone A has a plethora of beneficial biological effects. However, the pharmacokinetic (PK) data of yakuchinone A still remain unknown so far. Furthermore, the quantification of yakuchinone A in biological samples has not been reported in the literature. Therefore, in the present study we aimed to develop a new method for the fast, efficient and accurate assessment of yakuchinone A concentration in plasma, as a means for facilitating the PK evaluation of yakuchinone A. Results A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESIMS/ MS) method was developed and validated for the determination of yakuchinone A in rat plasma. Mass spectrometric and chromatographic conditions were optimized. Plasma samples were pretreated by protein precipitation with methanol. LC separation was performed on a Phenomenex Luna C18 column with gradient elution using a mobile phase consisting of methanol-water containing 0.5 mM formic acid (HCOOH) at a flow rate of 0.28 mL/min. ESI-MS spectra were acquired in positive ion multiple reaction monitoring mode (MRM). The precursor-to-product ion pairs used for MRM of yakuchinone A and yakuchinone B were m/z 313.1 → 137.0 and 311.2 → 117.1, respectively. Low concentration of HCOOH reduced the ion suppression caused by matrix components and clearly improved the analytical sensitivity. Yakuchinone A showed good linearity over a wide concentration range (r > 0.99). The accuracy, precision, stability and linearity were found to be within the acceptable criteria. This new method was successfully applied to analyze the rat plasma concentration of parent yakuchinone A after a single oral administration of SuoQuan capsules. Low systemic exposure to parent yakuchinone A was observed. Conclusion The proposed method is sensitive and reliable. It is hoped that this new method will prove useful for the future PK studies. [ABSTRACT FROM AUTHOR]

Highlights: [•] We developed and validated a novel LC–MS/MS method for imperialine quantification. [•] The method debuted on pharmacokinetic study of imperialine in rats. [•] Pharmacokinetic study was done at low doses (mg/kg, i.v., 5; p.o., 1, 5 and 10). [•] Oral bioavailability of 3 p.o. groups was 31.2%, 53.6% and 47.4%, respectively. [Copyright &y& Elsevier]

A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of timosaponin AIII (TA-III) in rat plasma, using ginsenoside Re as an internal standard (IS). TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer. The calibration curves were linear over the concentration ranges from 11.14 to 1114 ng/mL and the lower limit of quantification (LLOQ) was 11.14 ng/mL. Intra-day and inter-day precisions (RSD) were within 10%, and accuracy ranged from 6.4% to 9.1%. The extraction recovery at three concentrations ranged from 92.3% to 95.5%. The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration. The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III. [ABSTRACT FROM AUTHOR]