An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid(CGA) and taurocholic acid(TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatogra...An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid(CGA) and taurocholic acid(TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatographic separation was achieved on a Hedera ODS-2 column with a gradient elution using 10 mmol·L^(-1) of ammonium acetate buffer solution containing 0.5% of formic acid- acetonitrile as mobile phase at a flow rate of 300 μL·min-1. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration ranges of 0.1–10 ng·m L^(-1) for CGA and 2–150 ng·m L^(-1) for TCA. It was successfully applied to a pharmacokinetic study of CGA and TCA in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets(SBTs). In the single-dose study, the maximum plasma concentration(C_(max)), time to reach C_(max)(T_(max)) and elimination half-life(t_(1/2)) of CGA were(0.763 8 ± 0.542 0) ng·m L^(-1),(1.0 ± 0.5) h, and(1.3 ± 0.6) h, respectively. In the multiple-dose study, the C_(max), T_(max) and t_(1/2) of CGA were(0.663 7 ± 0.583 3) ng·m L^(-1),(1.1 ± 0.5) h, and(1.4 ± 0.7) h, respectively. For TCA, no significant characteristic increasing plasma TCA concentration-time curve was found in the volunteers after oral administration of SBTs, indicating its complicated process in vivo as an endogenous ingredient.展开更多
Type 2 diabetes mellitus(T2DM)therapy is facing the challenges of long-term medication and gradual destruction of pancreatic isletβ-cells.Therefore,it is timely to develop oral prolonged action formulations to improv...Type 2 diabetes mellitus(T2DM)therapy is facing the challenges of long-term medication and gradual destruction of pancreatic isletβ-cells.Therefore,it is timely to develop oral prolonged action formulations to improve compliance,while restoringβ-cells survival and function.Herein,we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property,which combined apical sodiumdependent bile acid transporter-mediated intestinal uptake and lymphatic transportation.In this system,taurocholic acid(TCA)modified poly(lactic-co-glycolic acid)(PLGA)was employed to achieve pancreas location,hydroxychloroquine(HCQ)was loaded to execute therapeutic efficacy,and 1,2-dilauroyl-sn-glycero-3-phosphocholine(DLPC)was introduced as stabilizer together with synergist(PLGA-TCA/DLPC/HCQ).In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction,thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day.In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress,remodeled the inflammatory pancreas microenvironment,and activated PI3K/AKT signaling pathway without obvious toxicity.This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.展开更多
基金supported financially by National Natural Science Foundation of China(No.81273482)the Graduate Innovation Fund of Zhejiang Huahai Pharmaceuticals Co.,Ltd
文摘An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid(CGA) and taurocholic acid(TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatographic separation was achieved on a Hedera ODS-2 column with a gradient elution using 10 mmol·L^(-1) of ammonium acetate buffer solution containing 0.5% of formic acid- acetonitrile as mobile phase at a flow rate of 300 μL·min-1. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration ranges of 0.1–10 ng·m L^(-1) for CGA and 2–150 ng·m L^(-1) for TCA. It was successfully applied to a pharmacokinetic study of CGA and TCA in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets(SBTs). In the single-dose study, the maximum plasma concentration(C_(max)), time to reach C_(max)(T_(max)) and elimination half-life(t_(1/2)) of CGA were(0.763 8 ± 0.542 0) ng·m L^(-1),(1.0 ± 0.5) h, and(1.3 ± 0.6) h, respectively. In the multiple-dose study, the C_(max), T_(max) and t_(1/2) of CGA were(0.663 7 ± 0.583 3) ng·m L^(-1),(1.1 ± 0.5) h, and(1.4 ± 0.7) h, respectively. For TCA, no significant characteristic increasing plasma TCA concentration-time curve was found in the volunteers after oral administration of SBTs, indicating its complicated process in vivo as an endogenous ingredient.
基金supported by National Natural Science Foundation of China(Nos.81972893,and 82172719)Excellent Youth Science Foundation of Henan province(212300410071,China)Training program for young key teachers in Henan Province(2020GGJS019,China)。
文摘Type 2 diabetes mellitus(T2DM)therapy is facing the challenges of long-term medication and gradual destruction of pancreatic isletβ-cells.Therefore,it is timely to develop oral prolonged action formulations to improve compliance,while restoringβ-cells survival and function.Herein,we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property,which combined apical sodiumdependent bile acid transporter-mediated intestinal uptake and lymphatic transportation.In this system,taurocholic acid(TCA)modified poly(lactic-co-glycolic acid)(PLGA)was employed to achieve pancreas location,hydroxychloroquine(HCQ)was loaded to execute therapeutic efficacy,and 1,2-dilauroyl-sn-glycero-3-phosphocholine(DLPC)was introduced as stabilizer together with synergist(PLGA-TCA/DLPC/HCQ).In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction,thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day.In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress,remodeled the inflammatory pancreas microenvironment,and activated PI3K/AKT signaling pathway without obvious toxicity.This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.