It is irrefutable that one of the most applicable medicines in the world is Nonsteroidal anti-inflammatory drugs (NSAIDs) owing to their prevalent use in reducing pain and fever. Also, it is used for the remedy of particular inflammatory illnesses. The fundamental mechanisms of most of the NSAIDs impelled hypersensitivity reactions to perform to be pharmacologically mediated which have been accompanied by the synthesis of Cysteinyl leukotriene (CysLTs) because of cyclooxygenase-1 inhibition, known as cross-reactive hypersensitivity. The formation of prostanoids which is also named prostaglandin-endoperoxide synthase (PTGS) was accomplished by Cyclooxygenase enzyme.
Prostaglandins H2 is generated from arachidonic acid in the presence of COX as a catalyzer in the first step in the biosynthesis of prostanoids. Prostaglandins H2 has an important role in the systematic in?ammation such as fatigue, fever, and pain and act on varied neurons. There are two kinds of this enzyme. The first one is the COX-1 which produces physiologically important prostaglandins, exists in healthy tissues. The second one is the COX-2 which contributes to inflammation and can be induced by extracellular or intracellular stimulants.
The first step in the synthesis of prostaglandins (PG) which occasions in?ammatory response from arachidonic acid which is catalyzed by COX-2. Although some of the NSAIDs are still selective on COX-2, most of them can impede COX enzyme activity on both COX-1 and COX-2 receptors. Celecoxib (CEL), 4-[5-(4-methyl phenyl)-3-(tri?uoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide, is a diaryl pyrazole the ?rst member of the Coxib group, a new NASID category, which was developed as an extra secure replacement of regular NSAIDs. This drug doesn’t make acute and chronic gastrointestinal toxicities and recognized as the first COX-2 selective inhibitor. Early research revealed that CEL has analgesic and anticancer effects too. CEL can be used in the curing of juvenile idiopathic arthritis, Ankylosing Spondylitis, osteoarthritis, rheumatoid arthritis, dysmenorrhea and cervical, colon and breast cancer. Ketoprofen (KET), (±)-(R, S)-2-(3-benzoylphenyl) propionic acid, belongs to NSAIDs, is used as a strong inhibitor of both lipo-oxygenase and cyclo-oxygenase, which also has analgesic and antipyretic effects. Physicochemical and structural features of ketoprofen caused deep penetration and accumulation in the inflammation centers and compatibility with other categories of drugs. The anti-inflammatory effect of ketoprofen is about 160 times that of aspirin. It has been consumed for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, bursitis, tendonitis, dysmenorrhea, and gout. Diclofenac (DIC), 2-[2,6dichlorophenylamino] benzene acetic acid is an aryl acetic derivatives and belongs to NSAIDs. It dissolves in water to a meager degree. DIC contains three effecting elements including anti-inflammatory, antipyretic and analgesic recognized by inhibiting prostaglandin synthesis through COX-2. The DIC absorption is occurred nearly completed with an absolute bioavailability of 89% when it is consumed orally, rectally and parenterally. It has been used for the treatment of juvenile idiopathic arthritis, Ankylosing Spondylitis, osteoarthritis, rheumatoid arthritis, dysmenorrhea, gout, and migraine. Meloxicam (MEL), 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol2-yl)-2H-1,2-benzothiazine-3- carboxamide 1,1-dioxide, is an enol carboxamide related Piroxicam and belongs to NSAIDs. It is capable to inhibit prostaglandin synthesis. Since the inhabitation of enzymatic activity of COX-2 is more than COX-1, MEL has a suitable anti-inflammatory effect. It also demonstrates antipyretic and analgesic effects. The drug is using for treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis. Insufficient solubility of MEL in the acidic medium may cause gastrointestinal side effects.In trace and ultra-trace analysis, preparation of the sample is the most effective and critical step during experimental setup. There are three main steps in sample preparation. First, delivery of analytes to the physical state which makes it possible to analyze them and determine their final values. Second, enrichment of the analytes to the desired values. Third, purification of the extracts before the instrumental analysis. Various techniques have been accomplished to achieve these intentions. Some of them are co-precipitation, solid phase extraction (SPE) and liquid-liquid extraction (LLE). These techniques are not cost-effective both on time consumption and an excessive requirement for sample and/or organic solvents and have inadequate separation parameters. New segmental and compact methods were developed to eliminate complex processes in which satisfactory preconcentration and separation are achieved. The SPE method has four advantages compare to LLE. The process is simpler, lower amounts of required solvents, a larger range of appropriate adsorbent, and at last more adequate separation parameters. So, this technique was widely utilized to preconcentrate and separate ultra-trace quantities of various inorganic and organic materials from intricate matrices. SPE methods are surface-dependent processes since their performance is directly influenced by the surface area and particle size of sorbent. Dispersive solid phase extraction (DSPE) is a modified method of usual SPE. It can be considered as a quick, easy, cheap, effective, rugged, and safe (QuEChERS) sample treatment technique. Unlike SPE, in DSPE the sorbent is added to the extract without any conditioning. The other advantage of DSPE is less sorbent requirement than SPE (about 50 mg). The dispersion was achieved by using external energy and lead to increase sorbent active surface. Therefore, extraction kinetics is improved, and a smaller amount of sorbent is required. Then, the centrifuge process is used to separate phases. At last, to achieve analytical data, recovering of sorbent is carried out. The spectroscopic technique is a usual analytical process. In this method, the sorbent surface is analyzed to evaluate analytes. In the other common method, the sorbent is eluted by a solvent for analytes desorption in order to perform an instrumental analysis. In 2013 Jamali et al. invented a modified DSPE method named solvent-assisted dispersive solid phase extraction (SADSPE). In SADSPE, the adequate amount of disperser solvent and sorbent were combined together. Then, the combination was injected quickly into the aqueous solution by means of a syringe to make a cloudy sample from the dispersion of tiny sorbent particles. Like conventional dispersive solid phase extraction methods, the solution phases were separated with the centrifuge method and the sedimented particles were eluted by a desorption solvent and then the analytes were quantified by instrumental analysis.In the current study, the SADSPE method was modified with using magnetic sorbent and ultrasonic waves which is named solvent-ultrasonic assisted magnetic dispersive solid phase extraction (SUAMDSPE). The adequate amounts of magnetic sorbent and disperser solvent were mixed together. Proper dispersion of the mixture was achieved by using ultrasonic waves. Then using syringe it was injected into the aqueous solution which contains proposed analytes. As soon as the mixture was added to the solution, a cloudy state was formed from the dispersion of fine sorbent particles. The sample was shaken gently, and the sorbent adsorbed analytes from the solution. In order to sediment these particles at the bottom of the testing vial, the vial was placed on a strong magnet. Then the decantation process was carried out and appropriate amounts of an organic solvent as the desorbing agent was added to the sediment phase under sonication. Then, the vial was placed on the magnet again, and the solvent was evacuated with a syringe and injected into the HPLC for quantitative and qualitative analysis. The SUAMDSPE is a cost-effective method since the technique is fast and easy to implement, low material is needed and also the separation factors of this technique are higher than conventional methods. The phase separation technique is the main advantage of this method towards SADSPE. In this method, a powerful magnetic field is used as an external force instead of centrifugation.