Study on Plasma Protein Binding Rate of Cajanonic Acid A with Different Species of Plasma by Ultrafiltration Combined with UPLC-MS/MS / 中国药房

OBJECTIVE： To compare plasma protein binding rate of cajanonic acid A with different species of plasma. METHODS：Using UPLC-MS/MS as the detection means. Plasma protein binding rate of low， medium and high concentrations of cajanonic acid A （2.5， 5， 20 μg/mL） with rats， rabbits and human plasma were determined by ultrafiltration method. The chromatographic conditions included that Waters BEH C18 as chromatographic column， WatersVanGuard BEH C18 as guard column， mobile phase consisted of ultrapure water solution containing 0.01％ formic acid （solvent A） and acetonitrile solution of 0.01％ formic acid （solvent B） gradient elution， at the flow rate of 0.15 mL/min， column temperature of 30 ℃， sample size of 2 μL. Mass spectrum condition included that ESI， negative ion mode acquisition， capillary voltage of 1.5 kV， cone voltage of 30 V， ion source temperature of 100 ℃， desolvent gas temperature of 400 ℃， cone gas flow of 50 L/h， desolvent gas flow of 800 L/h， scanning range of m/z 50→1 200. RESULTS： At the concentration of 2.5， 5 and 20 μg/mL， the plasma protein binding rates of cajanonic acid A were （75.63±0.90）％， （98.30±0.03）％ and （99.42±0.01）％ in the rats plasma； （79.61±1.08）％， （98.48±0.10）％ and （99.42±0.03）％ in rabbits plasma （n＝3）； （76.74±1.22）％， （97.99±0.11）％ and （99.37±0.01）％ in human plasma （n＝3）. At the concentration of 2.5 μg/mL， plasma protein binding rates of cajanonic acid A in plasma of rats and human were significantly lower than that in plasma of rabbits （P＜0.05）. CONCLUSIONS： The plasma protein binding rate of 5，20 μg/mL cajanonic acid A with rats， rabbits and human plasma are higher than that of 2.5 μg/mL cajanonic acid A. There is significant difference in plasma protein binding rate of 2.5 μg/mL cajanonic acid A with different species of plasma，and there is no significant difference in plasma protein binding rate of 5， 20 μg/mL cajanonic acid A with different species of plasma.

In vitro absorption mechanism of Erigeron breviscapus extract in Caco-2 cell monolayer model / 中国药理学通报

Aim To study the absorption mechanism of apigenin-7-O-glucronide, 3,4-Dihydroxycinnamic acid and chlorogenic acid in Erigeron breviscapus extract ( Ebe) by Caco-2 cell monolayer model. Methods The three active ingredients were quantified by UPLC-MS/MS method, and the effect of Ebe concentrations, conveying times, pH values and P-glycoprotein inhibi-tor on the transport of three active ingredients were also investigated. Results Apigenin-7-O-glucronide and chlorogenic acid in Caco-2 cell monolayer model were time-dependent and concentration-dependent. The 3, 4-Dihydroxycinnamic acid in Caco-2 cell uptake was concentration-saturate and P-glycoprotein inhibitor was involved in the uptake process. Conclusion The mechanism of apigenin-7-O-glucronide and chlorogenic acid absorption in cells is mainly through passive trans-port, and the absorption of 3, 4-Dihydroxycinnamic acid is mainly realized by the carrier transport.

Determination of daptomycin by UPLC-MS/MS and its pharmacokinetic eva-luation in critically ill patients / 中国药科大学学报

@#A sensitive, selective and simple liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method was developed for determining of daptomycinin human plasma and effluent. The analyte was extracted from plasma samples by SPE method, separated through a Phenomenex Kinetex C18 column(50 mm×2. 1 mm, 1. 7 μm)using isocratic mobile phase consisting of 0. 1% formic acid-acetonitile(75 ∶25), and analyzed by electro-spray ionization(ESI). The precursor to product ion transitions of m/z 810. 9→159. 1 and m/z 286. 2→217. 2 were used to measure daptomycinand the internal standard, respectively. The method was validated over a concentration range(plasma: 1-200 μg/mL, effulent: 0. 005-20 μg/mL). The intra- and inter-day precision values were less than 10% and accuracy values 90%-110%. The stability of daptomycinin human plasma and effluent under different storage conditions met the requirements of bioanalytical method. The concentration of daptomycin is significant lower in the septic shock patient, when give a dose of 6 mg/kg, the cmax and AUC0-24 h of steady state decreased by 50% and 60% respectively; the increase in capillary permeability and interstitial oedema during sepsis and septic shock may enhance drug distribution. By the way, daptomycin can be cleared via continuous veno-venous hemofiltration(CVVH)for nearly 16%. In summary, on the treatment of continuous renal replacement therapy(CRRT)in patients with septic shock with daptomycin therapy, the suggested dose should be increased, and the drug monitoring should be carried on.