Application of an LC-MS/MS Method to a Urinary Excretion Study of Triflusal and its Main Metabolite 2-hydroxy-4-trifluoromethyl Benzoic Acid in Human Urine

Objective: A validated liquid chromatography-tandem mass spectrometry method (LCMS/ MS) was established to simultaneously determine the concentration of triflusal and its main metabolite 2-hydroxy-4-trifluoromethyl benzoic acid(HTB) in human urine. Methods: The separation was performed on a Dikma C18 column using isocratic elution with acetonitrile-4 mmol/L ammonium acetate aqueous solution containing 0.3 % formic acid water (78: 28, V/V). The method involved extraction with methanol using protein precipitation. The precursor-toproduct ion transitions with multiple reaction monitoring was m/z 247.1→161.1, 204.8→106.7and 136.9→93.0 for triflusal, HTB and salicylic acid(IS), respectively. The method showed good linear relationships over the ranges of 0.08 to 48 μg/mL and0.5 to 50 μg/mL. Results: It was the first time that a urinary excretion study of triflusal capsule as oral. The cumulative urinary recovery showed 8.5% and 2.7% for triflusal and HTB, respectively. Conclusion: This method was successfully used for evaluating the pharmacokinetic properties of triflusal and HTB in urine in Chinese healthy subjects.

Simultaneous Determination of Columbianadin and Its Metabolite Columbianetin in Rat Plasma by LC-MS/MS: Application to Pharmacokinetics of Columbianadin after Oral Administration

Columbianadin and its metabolite columbianetin exhibited the anti-inflammatory, analgesic, calcium channel blocking and antitumor activities. To compare the differences between pharmacokinetics of columbianadin and its metabolite columbianetin after oral administration of pure columbianadin and Angelicae Pubescentis Radix (APR) extract, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated to simultaneously determine columbianadin and columbianetin in rat plasma. Two analytes and an internal standard (warfarin) were well separated and determined after liquid-liquid extraction with ethyl acetate. Ammonium acetate aqueous solution (1 mmol/L) and acetonitrile were used as the mobile phase and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) was 0.1 ng/mL for columbianetin and 0.5 ng/mL for columbianadin, respectively. There were significant differences between some pharmacokinetic parameters and bioavailability of columbianadin after oral administration of pure columbianadin and APR extract. The studies on comparative pharmacokinetics of columbianadin were of great use for facilitating the clinical application of columbianadin and were also highly meaningful for the potential development of APR.

Comparative Pharmacokinetics and Bioavailability of Three Ephedrines in Rat after Oral Administration of Unprocessed and Honey-Fried Ephedra Extract by Response Surface Experimental Design

Ephedra have been used as a common traditional Chinese medicine for thousands of years. However, the perspiration effect of the unprocessed ephedra was too strong. Clinical trials have shown that processing methods play a critical role in moderating the perspiration property of ephedra according to the needs. A LC-MS/MS method was developed and validated to compare the pharmacokinetic properties of the three ephedrines after oral administration of unprocessed and honey-fried ephedra extract. The contents of honey, frying temperature, and frying time were set at 20%, 116°C, and 7 min by the Box-Behnken response surface method, respectively. In the pharmacokinetics study, the biosamples were pretreated and extracted by protein precipitation method with acetonitrile and separated on an Agilent TC-C18column (250 mm × 4.6 mm, 5 μm) using a mobile phase consisting of 0.1% formic acid methanol and 5 mM ammonium acetate aqueous solution (5 : 95, v/v). All calibration curves were linear (r>0.9932) with lower limits of quantitation (LLOQs) < 12 ng/mL. The mean recoveries of the three analytes were higher than 75%. The pharmacokinetics study indicated that the reduced absorption of ephedrine hydrochloride (EH) and pseudoephedrine hydrochloride (PEH) in honey-fried ephedra group might be the main reason for the moderation of the diaphoretic property.

Transfer hydrodehalogenation of aryl halides accelerated by a saturated sodium acetate aqueous solution

A saturated sodium acetate aqueous solution could be applied as an efficient and environmentally-friendly reaction medium to accelerate transfer hydrodehalogenation of various aryl halides.

Influence of the Reaction Temperature on Cd1-xZnxS Thin Films with Chemical Bath Deposited

Cd1-xZnxS thin films were deposited on soda-lime glass substrates with chemical-bath deposition (CBD) using cadmium acetate, zinc sulfate, thiourea, ammonia and ammonium acetate aqueous solution at different with stirring. All the samples were annealed at 200 °C for 60 min in the air. The crystal structure, surface morphology, thickness and optical properties of Cd1-xZnxS thin films with increasing ammonia concentration were studied with X-ray diffraction (XRD), scanning electron microscopy (SEM), step height measurement instrument and spectrophotometer respectively. The results revealed that Cd1-xZnxS thin films had cubic crystal structure and the intensity of the diffraction peak decreased gradually as reaction temperature rose and the average crystal size was from 7.0 nm to 8.9 nm. All of Cd1-xZnxS thin films had a granular surface with some smaller pores. The Cd1-xZnxS thin films band gap was from 2.68 eV to 2.83 eV. The transmission of film deposited at 80 °C was highest. The suitable reaction temperature was from 70 °C to 80 °C.

DEVELOPMENT OF A FORCE FIELD FOR ARTEMISININ AND MOLECULAR DYNAMICS SIMULATION OF THE DISSOLUTION OF ARTEMISININ IN DIFFERENT SOLVENTS

Artemisinin is widely employed to treat malaria. A variety of experiments have been done to research the dissolution property of artemisinin in different solvents. To have an in-depth understanding of the property, it is essential to explore the dissolution property from molecular level with molecular dynamics (MD) simulation, which needs a satisfactory force field of artemisinin. Therefore in the research a quantum chemistry based force field was developed. The quantum chemical calculation at different levels was done and Hartree–Fock (HF) level calculation gives satisfactory results. The charge distribution was then determined successfully. The van der Waals (VDW) parameters of the C unit with sp3-C were tuned according to the difference between the dissolution enthalpy of artemisinin in ethanol and ethyl acetate. With the developed force field, MD method was employed to successfully simulate the dissolution property of artemisinin in different solvents. The simulation results show that artemisinin molecules tends to aggregate in water, while in the aqueous solution of ethanol, the same number of artemisinin molecules tends to disperse. Furthermore, simulation results show that 8 M ethyl acetate aqueous solution has better dissolution ability than 8 M ethanol aqueous. The simulation gave agreements with the experimental results.