Dataset Information

A High Throughput HPLC-MS/MS Method for Antihypertensive Drugs Determination in Plasma and Its Application on Pharmacokinetic Interaction Study with Shuxuetong Injection in Rats.

ABSTRACT: A high-throughput HPLC-MS/MS method was developed and validated for the determination of four antihypertensive drugs including metoprolol tartrate, hydrochlorothiazide, nifedipine, and valsartan in rat plasma. The Sprague-Dawley rats were randomly divided into three groups: A Group: gastric-administration of metoprolol tartrate, hydrochlorothiazide, nifedipine, or valsartan; B Group: a single intravenous injection of SXT, then dosing as the A group; C Group: daily injection of SXT through the tail vein for 8 consecutive days and dosing as the A group on the eighth day. For metoprolol tartrate and valsartan, blood samples were collected before administration and at time points 0.03, 0.08, 0.17, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h from the fossa orbitalis vein. For hydrochlorothiazide and nifedipine, the time points were 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, and 24 h. The plasma samples containing different individual antihypertensive drug were mixed and prepared by protein precipitation with methanol. The chromatographic separation was performed on an Agilent Eclipse Plus C18 column (2.1 mm×100 mm, 3.5 ?m) using gradient elution with mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). The flow rate was 0.3 mL/min. The detection was accomplished on a tandem mass spectrometer with an electrospray ionization (ESI) source by multiple reaction monitoring (MRM) in both positive and negative modes. The method was successfully applied to a pharmacokinetic interaction study of Shuxuetong injection on the antihypertensive drugs. The results suggested that SXT could increase the total amount of metoprolol tartrate and nifedipine in plasma and showed little influence on the pharmacokinetic behaviors of hydrochlorothiazide and valsartan.

SUBMITTER: Wei J

PROVIDER: S-EPMC6699285 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A High Throughput HPLC-MS/MS Method for Antihypertensive Drugs Determination in Plasma and Its Application on Pharmacokinetic Interaction Study with Shuxuetong Injection in Rats.

Wei Juan J Ma Wenjuan W Yao Guangzhe G Jia Qi Q Cheng Xuejing X Ouyang Huizi H Chang Yanxu Y Chen Xiaopeng X He Jun J

BioMed research international 20190806

A high-throughput HPLC-MS/MS method was developed and validated for the determination of four antihypertensive drugs including metoprolol tartrate, hydrochlorothiazide, nifedipine, and valsartan in rat plasma. The Sprague-Dawley rats were randomly divided into three groups: A Group: gastric-administration of metoprolol tartrate, hydrochlorothiazide, nifedipine, or valsartan; B Group: a single intravenous injection of SXT, then dosing as the A group; C Group: daily injection of SXT through the ta ...[more]

PMID: 31467909

Similar Datasets

Project description:Our previous work has shown a synergistic tumoricidal efficacy of combining the hexokinase (HK) inhibitor 2-deoxyglucose (2-DG) and the autophagy inhibitor chloroquine (CQ) through intraperitoneal injections on HK2-addicted prostate cancers in animal models. The pharmacokinetic (PK) behaviors of these oral drugs after simultaneous oral administration have not been reported. We developed high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analytical methods for 2-DG and the clinically favored drug hydroxychloroquine (HCQ) for sera samples. Using a jugular vein-cannulated male rat model with serial blood collection before and after a single gavage dose of each drug alone or in combination, we examined their PK metrics for drug-drug interactions. The data demonstrated a rapid and complete separation of 2-DG from common monosaccharides by HPLC-MS-MS multi-reaction monitoring. Application of the HPLC-MS-MS 2-DG and HCQ methods to sera samples of nine rats showed a peak time (Tmax ) for 2-DG of 0.5 h after 2-DG alone or with HCQ and identical post-peak half-life of approximately 1 h. With a seemingly bi-modal time course for HCQ, the Tmax for HCQ alone (1.2 h) was faster than that for the combination (2 h; p = .017). After combination dosing, the peak concentration (Cmax ) and area under the curve (AUC0-4h ) of 2-DG were decreased by 53.8% (p = .0004) and 53.7% (p = .0001), whereas AUC0-8h for HCQ was decreased by 30.8% (p = .0279) from the respective single dosing. Without changing the mean residence time (MRT0-∞ ) of each drug, the combination affected the apparent volume of distribution (Vd ) and clearance (CL) of 2-DG, and CL for HCQ without affecting its Vd . We observed significant negative PK interactions, probably at the intestinal absorption level, between 2-DG and HCQ taken simultaneously by mouth. Future optimization efforts are warranted for their combination regimen for clinical translation.

Dataset Information

A High Throughput HPLC-MS/MS Method for Antihypertensive Drugs Determination in Plasma and Its Application on Pharmacokinetic Interaction Study with Shuxuetong Injection in Rats.

Publications

A High Throughput HPLC-MS/MS Method for Antihypertensive Drugs Determination in Plasma and Its Application on Pharmacokinetic Interaction Study with Shuxuetong Injection in Rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets