Jinzhang Cai

Development of LC-MS determination method and back-propagation ANN pharmacokinetic model of corynoxeine in rat.

Corynoxeine(CX), isolated from the extract of Uncaria rhynchophylla, is a useful and prospective compound in the prevention and treatment for vascular diseases. A simple and selective liquid chromatography mass spectrometry (LC-MS) method was developed to determine the concentration of CX in rat plasma. The chromatographic separation was achieved on a Zorbax SB-C18 (2.1 mm × 150 mm, 5 μm) column with acetonitrile-0.1% formic acid in water as mobile phase. Selective ion monitoring (SIM) mode was used for quantification using target ions m/z 383 for CX and m/z 237 for the carbamazepine (IS). After the LC-MS method was validated, it was applied to a back-propagation artificial neural network (BP-ANN) pharmacokinetic model study of CX in rats. The results showed that after intravenous administration of CX, it was mainly distributed in blood and eliminated quickly, t1/2 was less than 1h. The predicted concentrations generated by BP-ANN model had a high correlation coefficient (R>0.99) with experimental values. The developed BP-ANN pharmacokinetic model can be used to predict the concentration of CX in rats.

Liquid chromatography mass spectrometry simultaneous determination of vindoline and catharanthine in rat plasma and its application to a pharmacokinetic study.

Vinblastine and vincristine, both of which are bisindole alkaloids derived from vindoline and catharanthine, have been used for cancer chemotherapy; their monomeric precursor molecules are vindoline and catharanthine. A simple and selective liquid chromatography mass spectrometry method for simultaneous determination of vindoline and catharanthine in rat plasma was developed. Chromatographic separation was achieved on a C18 (2.1 × 50 mm, 3.5 µm) column with acetonitrile-0.1% formic acid in water as mobile phase with gradient elution. The flow rate was set at 0.4 mL/min. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification. Mean recoveries were in the range of 87.3-92.6% for vindoline in rat plasma and 88.5-96.5% for catharanthine. Matrix effects for vindoline and catharanthine were measured to be between 95.3 and 104.7%. Coefficients of variation of intra-day and inter-day precision were both <15%. The accuracy of the method ranged from 93.8 to 108.1%. The method was successfully applied in a pharmacokinetic study of vindoline and catharanthine in rats. The bioavailability of vindoline and catharanthine were 5.4 and 4.7%, respectively.

Gradient elution liquid chromatography mass spectrometry determination of acetylcorynoline in rat plasma and its application to a pharmacokinetic study

Abstract 1. Acetylcorynoline is the major alkaloid component derived from Corydalis bungeana herbs. A sensitive and selective liquid chromatography mass spectrometry method for determination of acetylcorynoline in rat plasma was developed over the range of 5–1000 ng/mL to characterize the pharmacokinetic properties. 2. Chromatographic separation was achieved on a C18 (2.1 mm× 150 mm, 5 μm) column with acetonitrile 0.1% formic acid in water as mobile phase with gradient elution. The flow rate was set at 0.4 mL/min. After addition of carbamazepine as internal standard (IS), protein precipitation by acetonitrile–methanol (9:1, v/v) was used as sample preparation. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification using target ions m/z 410 for acetylcorynoline and m/z 237 for the IS. 3. Mean recoveries of acetylcorynoline in rat plasma were in the range of 72.3–87.6%. Matrix effects for acetylcorynoline were measured to be between 88.7% and 93.5%. Coefficient of variation of intra-day and inter-day precision were both <13%. The accuracy of the method ranged from 95.8% to 112.1%. The analyte was stable under auto-sampler, room temperature, freeze-thaw and long-term (20 days), the bias in concentration was within ±15% of their nominal values. 4. The LC-MS method for the determination of acetylcorynoline in rat plasma utilizing 100 µL of plasma with an LLOQ of 5.0 ng/mL developed and validated, it was sensitive, selective and simple. This method was successfully applied in pharmacokinetic study of acetylcorynoline after intravenous administration of single dosage 3 mg/kg in rats.

DETERMINATION OF ISOCORYNOXEINE IN RAT PLASMA BY LIQUID CHROMATOGRAPHY MASS SPECTROMETRY AND ITS APPLICATION

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of isocorynoxeine in rat plasma was developed. After addition of midazolam as internal standard (IS), sample preparation was performed by using liquid–liquid extraction with ethyl acetate. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 mm × 150 mm, 5 µm) column with acetonitrile-0.1% formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; selective ion monitoring (SIM) mode was used to quantify using target fragment ions m/z 383 for isocorynoxeine and m/z 326 for the IS. Calibration plots were linear over the range of 5–500 ng/mL for isocorynoxeine in plasma. Lower limit of quantification (LLOQ) for isocorynoxeine was 5 ng/mL. Mean recovery of isocorynoxeine from plasma was in the range of 93.6–96.6%. CV of intra-day and inter-day precision were both less than 15%. The newly developed method is simple, sensitive, and could function effectively in pharmacokinetic characterization of isocorynoxeine in rat plasma.

Determination of Rhynchophylline in Rat Plasma by Liquid Chromatography Mass Spectrometry and Its Application

A sensitive and selective liquid chromatography mass spectrometry method was developed for the determination of rhynchophylline in rat plasma. After the addition of estazolam as the internal standard (IS), protein precipitation by acetonitrile was used for sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 column (2.1 × 150 mm, 5 µm) with acetonitrile-0.1% formic acid as the mobile phase with gradient elution. The electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification by using target fragment ions m/z 385 for rhynchophylline and m/z 295 for the IS. Calibration plots were linear over the range of 5-500 ng/mL for rhynchophylline in plasma. The lower limit of quantification for rhynchophylline was 5 ng/mL. The mean recovery of rhynchophylline from plasma was in the range of 87.7-92.6%. The coefficients of variation of intra-day and inter-day precision were both less than 11%. This method is sensitive and selective enough to be used in pharmacokinetic research for the determination of rhynchophylline in rat plasma.

Determination of RKI-1447 in rat plasma by UPLC–MS/ms and investigation on its pharmacokinetics, an effective ROCK1 and ROCK2 inhibitor

RKI-1447 is an effective ROCK1 and ROCK2 inhibitor, having anti-invasion and anti-tumor activity. In this study, we used ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS...