The interest in therapeutic drug monitoring has increased over the last few years. Inter- and intra-patient variability in pharmacokinetics, plasma concentration related toxicity and success of therapy have stressed the need of frequent therapeutic drug monitoring of the drugs. A sensitive, selective and rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetylsalicylic acid (aspirin), salicylic acid, clopidogrel and carboxylic acid metabolite of clopidogrel in human plasma. The chromatographic separations were achieved on Waters Symmetry Shield(TM) C18 column (150 × 4.6 mm, 5 µm) using 3.5 mm ammonium acetate (pH 3.5)-acetonitrile (10:90, v/v) as mobile phase at a flow rate of 0.75 mL/min. The present method was successfully applied for therapeutic drug monitoring of aspirin and clopidogrel in 67 patients with coronary artery disease.
1. S007-867 is a novel antiplatelet agent that shows promising in vitro and in vivo efficacy. For further development and better pharmacological elucidation, we characterized pharmacokinetics and tissue distribution of S007-867 in a mouse model. 2. A sensitive, selective and robust LC-MS/MS method was developed and validated in the mouse plasma and tissue for quantification of S007-867. The chromatographic separation was performed on Waters Symmetry Shield C18 column (150 × 4.6 mm, 5 µm) using methanol and ammonium acetate buffer. 3. S007-867 was rapidly absorbed and distributed to various tissues. Following single oral administration of S007-867 in the mouse, the concentration was in the order of C intestine > C liver > C kidney > C heart > C spleen > C lungs > C brain. Tissue to plasma area under the plasma curve ratio suggested that the maximum amount of drug was found in the intestine and liver. Half life of S007-867 was found longer in the heart (8.08 h), spleen (∼ 7.94 h) and kidney (∼ 15.41 h) as compared with other tissues. 4. The preclinical pharmacokinetics and tissue distribution data obtained using this LC-MS/MS method are expected to assist the future clinical investigations of S007-867 as a promising antiplatelet agent.
Antimicrobial agents (AMAs) are widely exploited nowadays to meet the high demand for animal-derived food. It has a significant impact on the food chain whose end consumers are human beings. The burden of AMAs on humans comes from either meat or crops cultivated on soil containing high residual antibiotics, which are responsible for the global crisis of antibiotic resistance. Thus, the objective of this study was to design a selective and sensitive liquid chromatography−mass spectrometry (LC-MS)/MSbased simultaneous bioanalytical method for estimation of twenty AMAs in human plasma, raw meat, and soil samples. The selective extraction of all analytes from the above matrices was performed by the solid-phase extraction clean-up method to overcome the interferences. Analytes were separated on a Waters Symmetry Shield C18 (150 × 4.6 mm 2 , 5 μm) column, using an isocratic solvent system of methanol−0.5% formic acid (80:20, v/v) with 0.75 mL/min flow rate. The average extraction recoveries for all analytes in plasma were ranged from 42.0 to 94.0% with relative standard deviations (RSDs) below ±15%. All of the validation parameters are in accordance with the United State Food and Drug Administration (USFDA) guidelines. Moreover, the method was also valid for a broad plasma concentration range and can be proposed as an excellent method for routine pharmacokinetic studies, therapeutic drug monitoring, clinical analysis, and detection and quantitation of AMA remnants in raw meat as a standard quality control test for human consumption.
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