Das Sabya Sachi, Verma Priya Ranjan Prasad, Sekarbabu Viswanathan, Mohanty Satyajit, Pattnaik Ashok Kumar, Ruokolainen Janne, Kesari Kavindra Kumar, Singh Sandeep Kumar
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India.
School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun 248009, Uttarakhand, India.
ACS Omega. 2023 Mar 20;8(13):12456-12466. doi: 10.1021/acsomega.3c00429. eCollection 2023 Apr 4.
In the present study, we developed and validated a rapid, specific, sensitive, and reproducible liquid chromatography-electrospray ionization tandem mass spectrometry method for quantifying quercetin (QT) in rabbit plasma using hydrochlorothiazide as the internal standard. Animals were orally administered with optimized QT-loaded nanoemulsion (QTNE) and QT suspension (QTS), equivalent to 30 mg/kg, to the test and control group, respectively. The blood samples were collected at pre-determined time points up to 48 h. The linearity range was from 5 to 5000 ng mL with = 0.995. Further, we analyzed the various pharmacokinetic parameters and established the - correlation (IVIVC) of QTNE using GastroPlus software. The method was successfully developed and validated, and when applied for the determination of QT in rabbit plasma, it exhibited an increase in from 122.56 ng mL (QTS) to 286.51 ng mL (QTNE) (2.34-fold) and AUC from 976 ng h mL (QTS) to 4249 ng h mL (QTNE) (4.35-fold), indicating improved oral bioavailability QT when administered as QTNE. Statistical analysis revealed that the Loo-Riegelman method (two-compartmental method) best fitted the deconvolution approach ( = 0.998, SEP = 4.537, MAE = 2.759, and AIC = 42.38) for establishing the IVIVC. In conclusion, the established bioanalytical method and IVIVC studies revealed that QTNE is a potential carrier for the effective delivery of QT with enhanced oral bioavailability.
在本研究中，我们开发并验证了一种快速、特异、灵敏且可重复的液相色谱 - 电喷雾电离串联质谱法，以氢氯噻嗪为内标定量兔血浆中的槲皮素（QT）。分别给试验组和对照组动物口服剂量相当于30 mg/kg的优化槲皮素纳米乳剂（QTNE）和槲皮素混悬液（QTS）。在预定时间点采集血样，直至48小时。线性范围为5至5000 ng/mL，r = 0.995。此外，我们分析了各种药代动力学参数，并使用GastroPlus软件建立了QTNE的体内 - 体外相关性（IVIVC）。该方法成功开发并验证，用于测定兔血浆中的QT时，其Cmax从122.56 ng/mL（QTS）增加到286.51 ng/mL（QTNE）（2.34倍），AUC从976 ng·h/mL（QTS）增加到4249 ng·h/mL（QTNE）（4.35倍），表明以QTNE给药时QT的口服生物利用度提高。统计分析表明，Loo - Riegelman方法（二室模型法）最适合用于建立IVIVC的去卷积方法（r = 0.998，SEP = 4.537，MAE = 2.759，AIC = 42.38）。总之，所建立的生物分析方法和IVIVC研究表明，QTNE是有效递送QT并提高口服生物利用度的潜在载体。
