Simultaneous quantification of chlorogenic acid and taurocholic acid in human plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Shuanghua Baihe tablets

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.

Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment

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.