Application of graphitic sorbent for online microextraction of drugs in human plasma samples
Graphite-based microextraction by packed sorbent for online extraction of β-blockers from human plasma samples
Microextraction by packed sorbent (MEPS)
A new strategy for surface modification of polysulfone membrane by in situ imprinted sol-gel method for the selective separation and screening of L-Tyrosine as a lung cancer biomarker
Solid Phase Microextraction and Related Techniques for Drugs in Biological Samples
In drug discovery and development, the quantification of drugs in biological samples is an important task for the determination of the physiological performance of the investigated drugs. After sampling, the next step in the analytical process is sample preparation. Because of the low concentration levels of drug in plasma and the variety of the metabolites, the selected extraction technique should be virtually exhaustive. Recent developments of sample handling techniques are directed, from one side, toward automatization and online coupling of sample preparation units. The primary objective of this review is to present the recent developments in microextraction sample preparation methods for analysis of drugs in biological fluids. Microextraction techniques allow for less consumption of solvent, reagents, and packing materials, and small sample volumes can be used. In this review the use of solid phase microextraction (SPME), microextraction in packed sorbent (MEPS), and stir-bar sorbtive extraction (SBSE) in drug analysis will be discussed. In addition, the use of new sorbents such as monoliths and molecularly imprinted polymers will be presented.
Microextraction by packed sorbent: an emerging, selective and high-throughput extraction technique in bioanalysis
Sample preparation is an important analytical step regarding the isolation and concentration of desired components from complex matrices and greatly influences their reliable and accurate analysis and data quality. It is the most labor-intensive and error-prone process in analytical methodology and, therefore, may influence the analytical performance of the target analytes quantification. Many conventional sample preparation methods are relatively complicated, involving time-consuming procedures and requiring large volumes of organic solvents. Recent trends in sample preparation include miniaturization, automation, high-throughput performance, on-line coupling with analytical instruments and low-cost operation through extremely low volume or no solvent consumption. Micro-extraction techniques, such as micro-extraction by packed sorbent (MEPS), have these advantages over the traditional techniques. This paper gives an overview of MEPS technique, including the role of sample preparation in bioanalysis, the MEPS description namely MEPS formats (on- and off-line), sorbents, experimental and protocols, factors that affect the MEPS performance, and the major advantages and limitations of MEPS compared with other sample preparation techniques. We also summarize MEPS recent applications in bioanalysis.
Synthesis and biological evaluation of some new triazolo[1,5-a]quinoline derivatives as anticancer and antimicrobial agents
In the present study, versatile multifunctional unreported triazolo[1,5-a]quinoline derivatives were prepared. Compounds 1–19 were synthesized by adopting appropriate synthetic routes and were pharmacologically evaluated for their in vitro anticancer activity against human cancer cell lines: hepatocellular liver carcinoma (HEPG2) and Caucasian breast adenocarcinoma (MCF-7), in addition to their antibacterial and antifungal activities. Compound 4 demonstrated strong inhibitory effects against breast cancer (MCF-7), whereas compounds 8 and 19 exhibited moderate activity against breast carcinoma cell line MCF-7. Compounds 16 and 19 gave moderate activity against liver carcinoma cell line HEPG2. The antimicrobial activity of the prepared compounds was tested against bacteria and fungi. Among them, the results of antimicrobial activity indicated that compounds 4, 9, 11, 13, 15, 17, 18 and 19 were the most active compounds. Compound 4 exhibited strong activity against Fusarium sp., whereas compounds 9, 11, 15, 17, 18 and 19 showed high activity against Escherichia coli. More specifically, compound 17 displayed a high inhibitory effect against Bacillus cereus, Escherichia coli and Rhizoctonia sp.
Preparation of monolithic molecularly imprinted polymer sol–gel packed tips for high-throughput bioanalysis: Extraction and quantification of l-tyrosine in human plasma and urine samples utilizing liquid chromatography and tandem mass spectrometry
In situ monolithic molecularly imprinted polymer sol–gel packed tips (MMSTs) were prepared and evaluated for the extraction of lung cancer biomarker l-tyrosine (Tyr) from human plasma and urine samples. Several extraction parameters such as the conditioning, washing and elution solutions, pH and time were investigated. The enrichment factor (EF) and extraction recovery (ER) were studied. MMST showed good selectivity and a high extraction recovery, and MMST as a sorbent showed good stability and repeatability. The method validation showed good regression correlation coefficients for plasma and urine samples (R2 ≥ 0.996) within the concentration range of 5–1000 and 1–1000 nmol L−1 in plasma and urine samples, respectively. The lower limits of quantification (LLOQ) in the plasma and urine samples were 5 and 1 nmol L−1, respectively. The between-batch precision for Tyr in plasma ranged from 1.0 to 6.0%, and in urine it was from 1.0 to 7.0%. The results show that the developed method has more facility, stability, durability and repeatability compared with previous similar methods. To the best of our knowledge, this is the first study aimed at the selective separation of Tyr as a lung cancer biomarker by MMSTs from biological matrixes and detection by LC/MS/MS.
Advances and new technologies applied in controlled drug delivery system
A drug delivery system is defined as a formulation or a device that enables the introduction of a therapeutic substance into the body and improves its efficacy and safety by controlling the rate, time, and place of release of drugs in the body. This process includes the administration of the therapeutic product, the release of the active ingredients by the product, and the subsequent transport of the active ingredients across the biological membranes to the site of action. Drug delivery systems aim to improve patient compliance and convenience, such as, for example, fast-dissolving tablets. One of the most important goals of pharmaceutical science is localizing the pharmacological activity of the drug at the site of action. Drug delivery systems are molecular tools which, without undesired interactions at other sites, target a specific drug receptor. Keeping in view the advantages of the delivery system, rapidly disintegrating dosage forms have been successfully commercialized, and, because of increased patient demand, these dosage forms are expected to become more popular. Modern drug delivery technology has been made possible by advances in polymer science. These advances have resulted in polymers with unique properties. Drug delivery systems are made from a variety of organic and inorganic compounds such as polymers, lipids (liposomes, nanoemulsions, and solid–lipid nanoparticles), self-assembling amphiphilic molecules, dendrimers, and inorganic nanocrystals. In addition, hydrogels are novel delivery systems that have attracted much attention in current pharmaceutical research.
On-line detection of hippuric acid by microextraction with a molecularly-imprinted polysulfone membrane sorbent and liquid chromatography-tandem mass spectrometry
Destruction of sorbents during consecutive extractions using the micro-extraction packed sorbent (MEPS) technique is a serious problem. In MEPS the complex matrix such as plasma and blood can affect the sorbent physical properties and the sorbent can be deteriorated after handling of few samples. To overcome this problem, the surface of a polysulfone membrane (PSM) was modified by a molecularly imprinted sol-gel and utilized for online extraction of a lung cancer biomarker, hippuric acid (HA), in biological matrices. The molecularly imprinted polymer membrane provided fast, sensitive, selective and robust sample preparation method for HA in biological fluids. In addition, MIP membrane could be used for up to 50 extractions without a significant change in extraction recovery. To achieve the best results, the parameters that influenced the extraction efficiency were thoroughly investigated. Moreover, for evaluating the performance of the molecularly imprinted sol-gel membrane (MISM), a non-molecularly imprinted sol-gel membrane (NISM) as a blank was prepared. The limits of detection (LOD) and quantification (LOQ) for HA in both plasma and urine samples were 0.30 nmol L−1 and 1.0 nmol L−1; respectively. Standard calibration curves were obtained over the range of 1–1000 nmol L−1 for HA in plasma and urine samples. The coefficients of determination (R2) were ≥ 0.997. The extraction recoveries of HA from human plasma and urine samples were higher than 91%. The precision values for HA in plasma and urine samples were 2.2–4.8% and 1.1–6.7%; respectively.
A needle extraction utilizing a molecularly imprinted-sol–gel xerogel for on-line microextraction of the lung cancer biomarker bilirubin from plasma and urine samples
In the present work, a needle trap utilizing a molecularly imprinted sol–gel xerogel was prepared for the on-line microextraction of bilirubin from plasma and urine samples. Each prepared needle could be used for approximately one hundred extractions before it was discarded. Imprinted and non-imprinted sol–gel xerogel were applied for the extraction of bilirubin from plasma and urine samples. The produced molecularly imprinted sol–gel xerogel polymer showed high binding capacity and fast adsorption/desorption kinetics for bilirubin in plasma and urine samples. The adsorption capacity of molecularly imprinted sol–gel xerogel polymer was approximately 60% higher than that of non-imprinted polymer. The effect of the conditioning, washing and elution solvents, pH, extraction time, adsorption capacity and imprinting factor were investigated. The limit of detection and the lower limit of quantification were set to 1.6 and 5 nmol L−1, respectively using plasma or urine samples. The standard calibration curves were obtained within the concentration range of 5–1000 nmol L−1 in both plasma and urine samples. The coefficients of determination values (R2) were ≥0.998 for all runs. The extraction recovery was approximately 80% for BR in the human plasma and urine samples.