Development and validation of a high-performance liquid chromatography coupled with ultraviolet detection method for the determination of isocorydine in rat plasma and its application in pharmacokinetics.

A new HPLC-UV method has been developed, validated and applied for the determination of isocorydine (CAS 475-67-2) in rat plasma after oral or intravenous (i. v.) administration. Caffeine was used as the internal standard (IS). The analyte and IS were extracted from rat plasma by liquid-liquid extraction (LLE) with methyl tert-butyl ether and they were separated on an XTerra C18 column (250×4.6 mm, 5 µm, pH 1-12) with UV detection at 264 nm. The mobile phase consisted of methanol and 0.02 mol/L potassium dihydrogen phosphate-phosphoric acid buffer solution (pH 3.2) (30:70, v/v) at a flow rate of 1 mL/min for 8.5 min. The retention times of isocorydine and caffeine were approximately 6.5 and 5.1 min, respectively. The good linearity of the calibration curves was observed over the concentration range of 0.05-8 µg/mL (n=8, r 2≥0.9995). The lower limit of quantification (LLOQ) was 0.05 µg/mL [signal to noise ratio (S/N)≥10], and the limit of detection (LOD) was demonstrated as 0.01 µg/mL (S/N≥3). The mean extraction recovery ranged from 83.7% to 89.5% at 3 quality control (QC) concentrations. Intra-day and inter-day precision (relative standard deviation, RSD%) were within 4.7% and accuracy (relative error, RE%) ranged from -1.2% to 4.5%. The developed method was successfully applied to determination of the pharmacokinetic properties of isocorydine in rats after oral administration at a dose of 20 mg/kg and i. v. injection at 5 mg/kg.

Pharmacokinetic and myocardial enzyme profiles of two administration routes of epirubicin in breast cancer patients.

To evaluate the changes in myocardial enzymes and plasma epirubicin concentration following administration by micro-pump (MP) and intravenous drip (ID) in breast cancer patients.11 self-controlled breast cancer patients were recruited for a trial with epirubicin administration by MP for 48 h and by ID for 1 h during 2 cycles of treatment. Plasma concentration of epirubicin at different time points was determined using LC-MS/MS. The levels of myocardial enzymes before and after chemotherapy were compared. Another group of patients receiving epirubicin by ID (n=4) or MP (n=9) were monitored for 4 months.8 patients completed the self-controlled study. The peak concentration of epirubicin in the MP group and the ID group were 21.84±18.85 ng/mL and 294.80±225.54 ng/mL, respectively. The MP group had a longer duration (54~60 h) of plasma concentration of epirubicin not less than 10 ng/mL than that of the ID group (8~14 h). There was significant difference for the alteration of myocardial enzymes before and after chemotherapy (p<0.05) in the ID group, whereas the MP group showed no significant difference (p>0.05). The increased range of myocardial enzymes after chemotherapy in the ID group was larger than that of the MP group and the difference was significant (p<0.05). There is an increased cardiotoxicity in patients receiving epirubicin by ID during the 4-month trial.Administration of epirubicin by MP maintained an effective drug concentration for a longer period of time than by ID. The higher peak plasma concentration observed following epirubicin administration by ID may lead to cardiac toxicity.

Development and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of acrivastine and pseudoephedrine in human plasma and its application in pharmacokinetics.

A specific, sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of acrivastine and pseudoephedrine in human plasma samples. Plasma samples were processed and analyzed on a Phenomenex Luna 3 µ CN 100A column (150 mm×2.0 mm) eluted with the mobile phase consisting of methanol and 0.01 mol/L ammonium acetate water solution containing 0.1% formic acid (45:55, v/v) at a flow rate of 0.2 mL/min. The analytes were detected by positive ion electrospray ionization in multiple reaction monitoring mode. The transitions of m/z 349→278, m/z 166→148 and m/z 256→167 were monitored for acrivastine, pseudoephedrine and diphenhydramine (IS), respectively. The method was specific and sensitive with a lower limit of quantitation (LLOQ) of 1.52 ng/mL for acrivastine and 8.13 ng/mL for pseudoephedrine. The method showed good linearity in the range of 1.52~606.0 0 ng/mL for acrivastine and 8.13~813.12 ng/mL for pseudoephedrine (r≥0.996). The mean recovery were ranged 91.82% ~ 98.46% for acrivastine and 90.77% ~ 92.05% for pseudoephedrine. Validation results, such as accuracy, precision and repeatability were within the required limits. The method was successfully applied in a pharmacokinetic study of the acrivastine and pseudoephedrine hydrochloride compound capsule in humans.

Determination of the plasma pharmacokinetic and tissue distributions of swertiamarin in rats by liquid chromatography with tandem mass spectrometry.

An LC-MS/MS method was developed for the quantification of swertiamarin (CAS 17388-39-5) in rat plasma and tissues using gentiopicroside as the internal standard (IS). Swertiamarin and an IS were extracted from plasma and tissues by a simple solid-phase extraction (SPE) procedure. Separation was achieved on a Phenomenex kinetex-C18 column (100 mm×2.1 mm, 2.6 µm) with an isocratic mobile phase consisting of methanol and water (22:78, v/v) with 0.1% acetic acid at a flow rate of 0.2 mL/min. The analyte and IS were detected by negative ion electrospray ionisation in multiple-reaction monitoring mode while monitoring the transitions of m/z 433 [M + CH3COO] - →179 and m/z 415 [M + CH3COO] - →179 for swertiamarin and the IS, respectively. The method was validated with respect to selectivity, matrix effect, linearity, accuracy, precision, recovery and stability. The method was successfully applied in a pharmacokinetic study of swertiamarin after intravenous and oral administration to rats. The pharmacokinetics of swertiamarin showed rapid absorption and elimination, and its absolute bioavailability was low at 10.3%. After oral administration to rats, swertiamarin was rapidly and widely distributed in its tissues. High concentrations were found in the liver and kidney, indicating that swertiamarin was possibly absorbed in the liver and eliminated by the kidney.