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• A simple and sensitive UPLC-QqQ-MS/MS method for determing PNS in trace amount of rabbit tears was established. • The developed method was successfully applied for the pharmacokinetic study of PNS eye drop solution in rabbits. • This is the first pharmacokinetic study of PNS administration for eye drops. Panax notoginseng total saponins (PNS), the main bioactive components of the radix and rhizome of Panax notoginseng (Burk.) F.H. Chen, could treat eye disorders. For the treatment of ocular diseases, eye drops are the first choice with the most common, economic and good compliance. So we proposed that PNS might be able to treat inflammatory ocular surface diseases by eye drops based on its anti-inflammatory and antioxidant activities. The short elimination half-life (t 1/2) and rapid elimination of PNS after oral or intravenous administration may limit its application for eye disorders. Meanwhile, there is a lack of pharmacokinetic study on trace amount of tear samples with PNS eye drops. Therefore, a simple and sensitive ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method by multiple reaction monitoring (MRM) in positive ion mode was firstly developed and applied in the pharmacokinetic study of PNS in rabbit tears. Tears samples were prepared by protein precipitation using methanol. The linearity, limit of detection, limit of quantification, specificity, precision, repeatability, stability, recovery, and matrix effect have been investigated and passed their validation criteria. Compared with prior methods, this method has the advantages of rapid analysis, high sensitivity, simple sample preparation and less sample demands. The pharmacokinetic results indicated that PNS eye drops had a slower elimination and a longer t 1/2 by topical ocular administration, which is expected to improve the success rate of eye drops in the treatment of anterior segment diseases. The ocular pharmacokinetics of PNS provides an experimental guidance and feasibility basis for in vivo effect verification of PNS eye drops in the future investigation. [ABSTRACT FROM AUTHOR]

A simple and sensitive method for simultaneous derivatization and hollow fiber liquid phase microextraction (HF-LPME) followed by high performance liquid chromatography–fluorescence detection (HPLC–FL) to determine memantine hydrochloride (MT) in human plasma was developed. The derivatization and microextraction was combined to a single step to ensure the precision. What is more, the derivatization reaction accelerated the mass transfer during the process of microextraction. The hollow fiber was filled with cyclohexane and dansyl chloride (derivatization agent) as acceptor phase and submersed in the alkalinized plasma sample. The system was submitted to stirring at 800 rpm for 50 min at 40 °C. Different experimental parameters were systematically evaluated by response surface methodology. Under the optimized conditions, the calibration curve was linear in the range of 1–100 ng/mL ( r = 0.9991) with a limit of detection of 0.1 ng/mL ( S/N = 3). The precision estimated as the relative standard deviation (RSD) was less than 4.5% and the accuracy was 94.3–100.7%. The present method was successfully applied to determine MT in human plasma samples. [ABSTRACT FROM AUTHOR]

A novel and practical sample pretreatment method based on hollow fiber centrifugal ultrafiltration (HFCF-UF) was developed to determine plasma protein binding by using HPLC. The samples for analyzing unbound and total concentrations could be prepared in parallel simultaneously by the same device. It only required centrifugation for a short time and the filtrate could be injected directly for HPLC analysis without further treatment. Coumarins were selected as the model drugs. Acetone was chosen as the releasing agent to free the binding drug from the drug–protein complex for the total drug concentration determination. Non-specific bindings (NSBs) between the analytes and hollow fiber membrane materials were investigated. The type and volume of protein binding releaser were optimized. Additionally, centrifugal speed and centrifugal time were considered. Under the optimized conditions, the absolute recovery rates of the unbound and total concentrations were in the range of 97.5–100.9% for the three analytes. The limits of detection were in the range of 0.0135–0.0667 μg mL −1 . In vitro plasma protein binding of the three coumarins was determined at three concentrations using the validated method and the relative standard deviations (RSDs) were less than 3.4%. Compared with traditional method, the HFCF-UF method is simple to run, no specialized equipment requirement and is a more accurate plasma pretreatment procedure with almost excellent drug–protein binding equilibrium. Therefore, this method can be applied to determine the plasma protein binding in clinical practice. It also provides a reliable alternative for accurate monitoring of unbound or total drug concentration in therapeutic drug monitoring (TDM). [ABSTRACT FROM AUTHOR]

Graphene oxide (GO)-based dispersive solid phase extraction (D-SPE) method combined with multi-step preparation has been proposed for the evaluation of trace aflatoxins in proprietary Chinese medicines (PCM). After being extracted by methanol, the sample was purified based on multi-step preparation, including dehydration with MgSO 4 /NaCl and cleanup with neutral alumina. Then GO was used as an adsorbent in D-SPE method for further preconcentration of aflatoxins prior to high performance liquid chromatography-fluorescence detection. The selected conditions were investigated. The Box-Behnken design (BBD) was used to optimize factors affecting adsorption procedure. Under the optimized conditions, good linear relationships had been achieved with the correlation coefficient (R 2 ) varying from 0.9904 to 0.9990. The LODs and LOQs were ranging from 0.020 to 0.041 ng/mL and 0.061 to 0.125 ng/mL, respectively. The results of the recoveries were 74.0–102.7% for the four aflatoxins, while the precisions from 1.8% to 7.2% were obtained, which indicated that the method was suitable for the analysis of aflatoxins in PCM. [ABSTRACT FROM AUTHOR]

To examine how methods affect the evaluation of entrapment efficiency (EE) of liposomes, four different sample pretreatment methods were adopted in the experiment. The four sample pretreatment methods were size-exclusion chromatography (SEC), solid-phase extraction (SPE), centrifugation ultrafiltration (CF-UF) and hollow fiber centrifugal ultrafiltration (HF-CF-UF). Amphotericin B (AmB), which could self-associate to form aggregates in water is adopted as the model drugs in this paper. In the present work, it was found that the characterization results of four methods were quite different. The EE of liposome by SEC was about 93%, only 5–13% using C 18 or HLB columns, and approximately 100% by CF-UF. The EE of HF-CF-UF reached up to nearly 99.0%. Further, this paper revealed the reasons making the difference of EE among four methods. Conventional SEC may distort the authentic of EE of liposomes with mainly employing some small liposomes or excessive water as eluent. For SPE, cholesterol on liposome surface could interact with the stationary phase making it hard to elute with water, and increase the risk of liposome leakage. While for CF-UF, concentration polarization was a main limitation hindering unentrapped drug to pass through membrane, making unentrapped drug undetectable in liposome. HF-CF-UF could truly reflect EE of liposomes with the concentration of unentrapped AmB lower than 25.0 μg/mL. However, when the concentration was higher than 25.0 μg/mL, AmB aggregates could be entrapped by hollow fiber. From the above analysis, this paper came to the conclusion that each method had its own feature in characterization. This study provided a reasonable guideline for choosing methods to character the EE of liposome. [ABSTRACT FROM AUTHOR]

Highlights: [•] A method for determination of 12 illicit drugs in urine and blood was developed. [•] The present method combined SPE with UPLC–ESI-MS/MS. [•] The proposed method is simple and fast. [•] Extremely low detection limit was achieved. [•] It is reliable and robust for drug screening in forensic toxicological analysis. [ABSTRACT FROM AUTHOR]

Highlights: [•] It was reported that not all ILs performed ideal headspace efficiency by HS-GC. [•] The relationship between ILs and organic solvents was first investigated. [•] It provided a guidance to choose ILs for analytes as the matrix medium by HS-GC. [Copyright &y& Elsevier]