Nonsteroidal Anti-inflammatory Drugs Concentration Research Articles

Facile and efficient preparation of amino bearing metal-organic frameworks-coated cotton fibers for solid-phase extraction of non-steroidal anti-inflammatory drugs in human plasma

The determination of blood concentration of non-steroidal anti-inflammatory drugs (NSAIDs) is highly desired in clinical practice. In this work, three amino bearing metal-organic frameworks (amino-MOFs) coated cotton fibers were prepared using a facile cysteine-triggered in situ growth strategy and proposed as in-tip solid-phase microextraction (in-SPME) adsorbents for efficient extraction of non-steroidal anti-inflammatory drugs from human plasma. The self-made adsorbents exhibited satisfactory extraction performance toward three NSAIDs including diclofenac sodium, ketoprofen and flurbiprofen. Under the optimized conditions, the established method exhibited satisfactory enrichment performance, low limits of detection and excellent extraction efficiency. Good reproducibility, wide linear range, excellent linearity and satisfactory sensitivity were obtained in the experiment. The method was also used for the enrichment and determination of NSAIDs in human plasma samples. Good recoveries were obtained, ranging from 66.5% to 98.9% with relative standard deviations less than 6.62%. The good performance of amino-MOFs was due to the synergistic effects arising from grafted charged amino groups within ordered pores of suitable size, leading to strong affinity towards guest molecules. Electrostatic interaction, hydrogen bond and π-π interaction played a vital role in the extraction of NSAIDs. This report indicated the potential of amino-MOFs as efficient adsorbents for the determination of NSAIDs from human plasma.

Determination and risk assessment of pharmaceutical residues in the urban water cycle in Selangor Darul Ehsan, Malaysia.

The environmental fate of non-steroidal anti-inflammatory drugs (NSAIDs) in the urban water cycle is still uncertain and their status is mainly assessed based on specific water components and information on human risk assessments. This study (a) explores the environmental fate of NSAIDs (ibuprofen, IBU; naproxen, NAP; ketoprofen, KET; diazepam, DIA; and diclofenac, DIC) in the urban water cycle, including wastewater, river, and treated water via gas chromatography-mass spectrophotometry (GCMS), (b) assesses the efficiency of reducing the targeted NSAIDs in sewage treatment plant (STP) using analysis of variance (ANOVA), and (c) evaluates the ecological risk assessment of these drugs in the urban water cycle via teratogenic index (TI) and risk quotient (RQ). The primary receptor of contaminants comes from urban areas, as a high concentration of NSAIDs is detected (ranging from 5.87 × 103 to 7.18 × 104 ng/L). The percentage of NSAIDs removal in STP ranged from 25.6% to 92.3%. The NAP and KET were still detected at trace levels in treated water, indicating the persistent presence in the water cycle. The TI values for NAP and DIA (influent and effluent) were more than 1, showing a risk of a teratogenic effect. The IBU, KET, and DIC had values of less than 1, indicating the risk of lethal embryo effects. The NAP and DIA can be classified as Human Pregnancy Category C (2.1 > TI ≥ 0.76). This work proved that these drugs exist in the current urban water cycle, which could induce adverse effects on humans and the environment (RQ in high and low-risk categories). Therefore, they should be minimized, if not eliminated, from the primary sources of the pollutant (i.e., STPs). These pollutants should be considered a priority to be monitored, given focus to, and listed in the guideline due to their persistent presence in the urban water cycle.

Removal of Non-Steroidal Anti-Inflammatory Drugs from Drinking Water Sources by GO-SWCNT Buckypapers.

Pharmaceutical products such as antibiotics, analgesics, steroids, and non-steroidal anti-inflammatory drugs (NSAIDs) are new emerging pollutants, often present in wastewater, potentially able to contaminate drinking water resources. Adsorption is considered the cheapest and most effective technique for the removal of pollutants from water, and, recently, membranes obtained by wet filtration method of SWCNT aqueous solutions (SWCNT buckypapers, SWCNT BPs) have been proposed as self-standing porous adsorbents. In this paper, the ability of graphene oxide/single-walled carbon nanotube composite membranes (GO-SWCNT BPs) to remove some important NSAIDs, namely Diclofenac, Ketoprofen, and Naproxen, was investigated at different pH conditions (pH 4, 6, and 8), graphene oxide amount (0, 20, 40, 60, and 75 wt.%), and initial NSAIDs concentration (1, 10, and 50 ppm). For the same experimental conditions, the adsorption capacities were found to strongly depend on the graphene oxide content. The best results were obtained for 75 wt.% graphene oxide with an adsorption capacity of 118 ± 2 mg g-1 for Diclofenac, 116 ± 2 mg g-1 for Ketoprofen, and 126 ± 3 mg g-1 for Naproxen at pH 4. Overall, the reported data suggest that GO-SWCNT BPs can represent a promising tool for a cheap and fast removal of NSAIDs from drinking water resources, with easy recovery and reusability features.

Non-steroidal anti-inflammatory drugs caused an outbreak of inflammation and oxidative stress with changes in the gut microbiota in rainbow trout (Oncorhynchus mykiss)

One of the main contributors to pharmaceutical pollution of surface waters are non-steroidal anti-inflammatory drugs (NSAIDs) that contaminate the food chain and affect non-target water species. As there are not many studies focusing on toxic effects of NSAIDs on freshwater fish species and specially effects after dietary exposure, we selected rainbow trout (Oncorhynchus mykiss) as the ideal model to examine the impact of two NSAIDs – diclofenac (DCF) and ibuprofen (IBP). The aim of our study was to test toxicity of environmentally relevant concentrations of these drugs together with exposure doses of 100× higher, including their mixture; and to deepen knowledge about the mechanism of toxicity of these drugs. This study revealed kidneys as the most affected organ with hyalinosis, an increase in oxidative stress markers, and changes in gene expression of heat shock protein 70 to be signs of renal toxicity. Furthermore, hepatotoxicity was confirmed by histopathological analysis (i.e. dystrophy, congestion, and inflammatory cell increase), change in biochemical markers, increase in heat shock protein 70 mRNA, and by oxidative stress analysis. The gills were locally deformed and showed signs of inflammatory processes and necrotic areas. Given the increase in oxidative stress markers and heat shock protein 70 mRNA, severe impairment of oxygen transport may be one of the toxic pathways of NSAIDs. Regarding the microbiota, an overgrowth of Gram-positive species was detected; in particular, significant dysbiosis in the Fusobacteria/Firmicutes ratio was observed. In conclusion, the changes observed after dietary exposure to NSAIDs can influence the organism homeostasis, induce ROS production, potentiate inflammations, and cause gut dysbiosis. Even the environmentally relevant concentration of NSAIDs pose a risk to the aquatic ecosystem as it changed O. mykiss health parameters and we assume that the toxicity of NSAIDs manifests itself at the level of mitochondria and proteins.

From the pills to environment – Prediction and tracking of non-steroidal anti-inflammatory drug concentrations in wastewater

The extend of environment pollution by pharmaceuticals is in a stage that required more automatic and integrated solutions. The non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most popular pharmaceutical in the world and emerging pollutants of natural waters. The aim of the paper was to check the correlation of the sales data of selected NSAIDs (ibuprofen, naproxen, diclofenac) and their concentration in the WWTP in order to enable predicting their loads, having only the sales data. For calculations, we apply three discharge scenarios (the fates between purchased to the presence in influents), having in mind that some part of sold mass can be improperly dispose to sewage system. To support predictions, chemical analysis was conducted in two conventional wastewater treatment plants (WWTPs) located in Poland during 2018 and 2020, thereby before and during pandemic situation. The NSAIDs concentration in the influent was higher than that which would be obtained if all of the administrated mass of the pharmaceutical went through the metabolic pathway of transformation. This means that substantial mass of sold NSAIDs in improperly dispose to sewage system, and this factor need to be taken into account in future predictions. Furthermore, results indicate that the variance of naproxen and diclofenac concentrations in the influent has no correlation with relatively stable sales throughout whole year. The pandemic situation had yet no direct effect to diclofenac concentrations in influents, despite observed increasing of sales. It was calculated that more than 60 kg of diclofenac was discharged into the Baltic Sea in 2018, and 20 kg in the first half of 2021 from two tested WWTPs. The presence of 4OH-diclofenac in effluents often in higher concentration compared to diclofenac mean that this still biologically active compound need to be taken into account in future risk assessment.

Enhanced Removal of Non-Steroidal Inflammatory Drugs from Water by Quaternary Chitosan-Based Magnetic Nanosorbents

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common pharmaceuticals used worldwide. They are widely detected in natural waters due to their persistence in wastewater treatment, and their removal is desirable in wastewater management. As a contribution to tackle this challenge, this study explores magnetic quaternary chitosan-based nanosorbents for the effective magnetically assisted removal of three NSAIDs (diclofenac, naproxen, and ketoprofen) from water. Toward this goal, silane groups were grafted onto the backbone of trimethyl chitosan through the reaction with an epoxide functionalized silane. Once silanized, the modified chitosan was employed to coat Fe3O4 nanoparticles. The prepared materials were characterized using FTIR spectroscopy and solid-state 29Si and 13C NMR spectroscopy, which confirmed the encapsulation of Fe3O4 nanoparticles with a hybrid siliceous material enriched in trimethyl chitosan. The effect of the initial NSAIDs concentration, pH, and contact time in the adsorption behavior was investigated. The kinetic data were well described by the pseudo-second-order kinetic model, indicating a chemisorption mechanism. The maximum adsorption capacities estimated from the Langmuir model were 188.5 mg/g (0.5925 mmol/g), 438.1 mg/g (1.7371 mmol/g), and 221.5 mg/g (0.8710 mmol/g) for diclofenac, naproxen, and ketoprofen, respectively. These adsorption capacities are higher than those of most reported sorbents, indicating the potential of these biosorbents to remove the selected NSAIDs using low-energy magnetically assisted separation.

Application of the model of cylindrical reactor for self-purification by indigenous microorganisms

Pharmaceutically active compounds (PhACs), in particular, nonsteroidal antiinflammatory drugs (NSAIDs) are in increasingly wider usage, and as such are more and more frequently part of the organic matter of recipient rivers, especially in their lower courses. To indicate their significance as pollutants, as well as the significant role that the presence of autochthonous microflora plays in solving this issue, we undertook to perform this experiment. The experiment, titled ?Application of the model of cylindrical reactor in self-purification by indigenous microorganisms?, was conducted during a one-year period at the location of Vukovci, in the lower course of the Moraca river. Assuming that the concentration of NSAIDs and PhACs in water can be reduced through selfpurification, it has been proven that such processes result in a modification of phenotype in the indigenous microbiological population. Having the abovementioned premise in mind, we constructed the experiment model, which entails kineticism of water, whereas the defined volume flow rate per unit time was 0.005 m/s, through the known distance of 432 m. Over one year of application of the model of the cylindrical reactor for enhancing self-purification capacity by indigenous microorganisms, auto-purification increased by 28.05%, the phenotype of the indigenous microorganisms changed by 24.62%, whereas the total concentration of particular PhACs, micropollutants, and NSAIDs decreased by 4.19%.

Comparison of Skin Permeation and Putative Anti-Inflammatory Activity of Commercially Available Topical Products Containing Ibuprofen and Diclofenac.

PurposeThe therapeutic effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs) depends on the drug’s ability to penetrate and permeate the skin and subsequently inhibit cyclo-oxygenase (COX) isoforms responsible for pain and inflammation. Most commercially available topical NSAID formulations are clinically effective, but direct comparisons of anti-inflammatory activity including both skin absorption and inhibitory potency are lacking. This study examined the skin absorption of representative commercially available topical diclofenac- and ibuprofen-based formulations along with published potency values to determine formulations with superior anti-inflammatory activity.Materials and MethodsCumulative absorption and flux profiles of 12 commercially available topical NSAIDs (6 diclofenac-based and 6 ibuprofen-based) were evaluated in vitro using human skin in static Franz diffusion cells. Each formulation was applied as a single dose. In vitro permeation parameters and published COX-2 inhibition values were used to calculate a modified index of topical anti-inflammatory activity (mITAA).ResultsAll diclofenac and ibuprofen formulations permeated human skin in vitro. The rate and degree of absorption differed between diclofenac and ibuprofen formulations and between formulations of the same drug. NSAID concentration within a product was not solely responsible for the permeation flux or degree of absorption. Ibuprofen formulations permeated the skin more rapidly and to a greater degree than diclofenac, but calculated mITAAs were higher for diclofenac.ConclusionDiclofenac exhibited superior anti-inflammatory activity as measured by the index. Differences beyond drug concentration, including excipients, drug salt form, and dosage form, contribute to differences in absorption and thus in anti-inflammatory activity. Both absorption and COX-2 inhibition potency are important for anti-inflammatory activity, but their priority depends upon the products being compared—with the same NSAID, absorption determines superiority; with different NSAIDs, superiority is determined by the balance between absorption and COX-2 potency. These findings should be considered when selecting a topical NSAID for treating patient pain and inflammation.

Occurrence and environmental risks of nonsteroidal anti-inflammatory drugs in urban wastewater in the southwest monsoon region of India.

Municipal wastewater treatment plants (MWWTPs) are considered to reduce the amount of pollutants that enter water reservoirs as a result of wastewater disposal. An assessment of the occurrence and removal of pharmaceutical compounds, mainly nonsteroidal anti-inflammatory drugs (NSAIDs), in wastewater from the Kavoor MWWTP (southwest monsoon region), India, is presented in this paper. The performance of the MWWTP was monitored in the summer (May) and monsoon (September) periods. The highest inlet concentrations of diclofenac, naproxen, ibuprofen, ketoprofen, and acetylsalicylic acid in the wastewater were observed in May and were 721.37, 2132.48, 2109.875, 2747.29, and 2213.36μg/L, respectively. The ketoprofen content was found to be higher than that of other NSAIDs in the influent in both seasons, whereas the diclofenac content was found to be the lowest. The removal efficiency (RE) of the target NSAIDs in the Kavoor secondary treatment plant varied from 81.82-98.92% during the summer season. During the monsoon season, the influent NSAID concentration level dropped, probably because of infiltration in old sewer pipes. In addition, a 100% RE was achieved for all the target NSAIDs in the wastewater of the MWWTP. The results showed that secondary treatment plants have the potential to remove NSAID compounds from municipal sewage with consistent performance. The environmental hazards caused by the accumulation of such compounds in water reservoirs are due to open discharge. The environmental risk levels of these compounds were also studied by the environmental risk assessment (ERA) using the European Agency for Evaluation of Medicines approach.

VITREOUS PROSTAGLANDIN E2 CHANGES AFTER TOPICAL ADMINISTRATION OF DICLOFENAC 0.1%, INDOMETHACIN 0.5%, NEPAFENAC 0.3%, AND BROMFENAC 0.09.

To evaluate the vitreous concentration of different nonsteroidal anti-inflammatory drugs (NSAIDs) after topical administration and the related prostaglandin E2 (PGE2) levels in patients undergoing pars plana vitrectomy. A prospective, randomized, investigator-masked study was performed. One hundred four patients scheduled for a pars plana vitrectomy for an epiretinal membrane or a macular hole were randomized to receive topical diclofenac 0.1%, indomethacin 0.5%, nepafenac 0.3%, bromfenac 0.09%, or placebo 3 days before surgery. At the beginning of surgery, a sample of undiluted vitreous was collected in each patient to assess NSAIDs concentration and PGE2 levels. The median vitreous concentrations were 203.35 (interquartile range 146.54-264.18) pg/mL for diclofenac, 243.45 (interquartile range 156.96-365.37) pg/mL for nepafenac, 438.21 pg/mL (interquartile range, 282.52-645.87) for its active metabolite amfenac, 350.14 (interquartile range, 290.88-481.95) pg/mL for indomethacin, and 274.59 (245.43-358.25) pg/mL for bromfenac. Vitreous PGE2 levels were significantly lower for all the NSAIDs groups compared with the control group (P < 0.001). A statistically significant higher vitreous PGE2 level was found in the diclofenac group compared with the other NSAIDs groups (P < 0.05). Topical NSAIDs achieve sufficient vitreous concentration to decrease vitreous PGE2 levels compared with the control group. The different efficacy in reducing PGE2 concentration may affect the management of posterior segment inflammation.

Effects of NSAIDs on the nanoscopic dynamics of lipid membrane

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for their antipyretic, anti-inflammatory, and painkiller actions despite a wide spectrum of side effects. The mechanisms involved in their therapeutic actions and side-effects have not been clearly understood yet. The assertion that effects of NSAIDs are related to their action at cellular membrane level has stimulated the investigation of interaction between NSAIDs and membranes. Here, we report effects of two different NSAIDs, ibuprofen and indomethacin, on the thermotropic phase behaviour and the dynamics of DMPC membrane as studied using neutron scattering techniques. Elastic intensity scan measurements showed that both drugs substantially alter the phase behaviour of the membrane. However, the effects of these drugs are found to differ quantitatively, which is correlated with their respective interactions with phospholipid membrane. Quasielastic neutron scattering measurements showed that in the ordered phase, both drugs enhance the dynamics of the membrane, but the drugs' effects on the membrane dynamics differ in the fluid phase. Indomethacin suppresses the dynamics of the membrane, whereas ibuprofen does not show significant effect at the same molar concentration. We have also investigated the effect of concentration of ibuprofen on the dynamics of the membrane. Our measurements provide clear evidence that interaction of NSAID with the membrane depends on both the physical state of the membrane and the nature and concentration of NSAID. Hence, one must investigate each NSAID independently while analysing its action mechanism. Better understanding of NSAID-membrane interaction can pave the way for designing more effective NSAID with reduced side effects.

Evaluation of the photosynthetic parameters, emission of volatile organic compounds and ultrastructure of common green leafy vegetables after exposure to non-steroidal anti-inflammatory drugs (NSAIDs).

Understanding the effects of many essential non-steroidal anti-inflammatory drugs (NSAIDs) on plants is still limited, especially at environmentally realistic concentrations. This paper presents the influence of three of the most frequently used NSAIDs (diclofenac, ibuprofen, and naproxen) at environmentally realistic concentrations on the autochthonous green leafy vegetables: orache (Atriplex patula L.), spinach (Spinacia oleracea L.) and lettuce (Lactuca sativa L.). Our research was focused on the determination of the photosynthetic parameters, the emission rate of volatile organic compounds, and the evaluation of the ultrastructure of leaves of studied vegetables after exposure to abiotic stress induced by environmental pollutants, namely NSAIDs. The data obtained indicate a moderate reduction of foliage physiological activity as a response to the stress induced by NSAIDs to the selected green leafy vegetables. The increase of the 3-hexenal and monoterpene emission rates with increasing NSAIDs concentration could be used as a sensitive and a rapid indicator to assess the toxicity of the NSAIDs. Microscopic analysis showed that the green leafy vegetables were affected by the selected NSAIDs. In comparison to the controls, the green leafy vegetables treated with NSAIDs presented irregular growth of glandular trichomes on the surface of the adaxial side of the leaves, less stomata, cells with less cytoplasm, irregular cell walls and randomly distributed chloroplasts. Of the three NSAIDs investigated in this study, ibuprofen presented the highest influence. The results obtained in this study can be used to better estimate the impact of drugs on the environment and to improve awareness on the importance of the responsible use of drugs.

Nickel-iron layered double hydroxide nanostructures for micro solid phase extraction of nonsteroidal anti-inflammatory drugs, followed by quantitation by HPLC-UV.

Layered double hydroxides (LDHs) of nickel and iron were hydrothermally prepared by co-precipitation using urea hydrolysis. The Ni-Fe LDH nanostructures were characterized by X-ray diffraction, FT-IR spectroscopy, scanning electron microscopy, thermogravimetric and energy dispersive X-ray analysis. The LDHs are shown to be a viable sorbent for micro solid phase extraction by packed sorbent of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, mefenamic acid and naproxen from human urine. Adsorption and desorption parameters were optimized using a central composite design. Following desorption with a methanol/water mixture (95:5 v:v) containing 0.1% formic acid, the NSAIDs were quantified by HPLC with UV detection. Under the optimal conditions, response is linear in the 10-1000ng.mL-1 NSAID concentration range. Limits of detection and intra-day and inter-day RSDs are <10ng.mL-1 and 10.2%, respectively. The method was successfully applied to the determination of NSAIDs in some positive human urine samples. Relative recoveries from spiked samples range from 94.8 to 113%. Graphical abstract Layered double hydroxides of nickel and iron were synthesized and packed in a spinal syringe for micro solid phase extraction of non-steroidal anti-inflammatory drugs.

Bio-electro-Fenton process for the degradation of Non-Steroidal Anti-Inflammatory Drugs in wastewater

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are ubiquitous municipal wastewater pollutants of which several are resistant to degradation in conventional wastewater treatment, and represent a major environmental health concern worldwide. An alternative treatment, the bio-electro-Fenton process, has received increasing attention in past years. In this process the strong oxidant HO is formed using the electrons derived from bacterial oxidation of organic substrate. In this work, a laboratory scale microbial electrolysis cell based bio-electro-Fenton process was developed for the treatment of four different NSAIDs. The system was demonstrated to remove low concentration NSAIDs from water and wastewater and all tested parameters (cathode pH, cathode air-flow, cathode Fe2+ concentration, applied voltage, NSAIDs concentration and reaction time) were found to affect the apparent first order rate constant and removal efficiency for NSAIDs. Optimum parameter values were found to be pH = 2, Fe+2 = 7.5 mM, air-flow = 8 mL min−1, applied voltage = 0.3 V; the apparent rate constant was higher for higher NSAIDs initial concentration. For reaction times of 5 h removal efficiencies were 59–61% for Ketoprofen, 87–97% for Diclofenac, 80–86% for Ibuprofen and 75–81% for Naproxen. Prolonged reaction times lead to substantial increase in removal efficiencies for Ketoprofen and Naproxen. Finally results obtained with real wastewater show lower removal rate constants than with distilled water matrices suggesting interference from wastewater components in the NSAIDs oxidation process. The results offer insight into future developments of an efficient platform for wastewater treatment technology targeting micropollutants.

Assessment of nonsteroidal anti-inflammatory drugs by ultrasonic-assisted extraction and GC-MS in Mgeni and Msunduzi river sediments, KwaZulu-Natal, South Africa.

The occurrence of eight pharmaceuticals was monitored during four seasons (spring, summer, autumn, and winter) along a 250-km stretch of the Msunduzi and Mgeni rivers in KwaZulu-Natal, South Africa. This paper describes an optimized method for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in sediments. The method combines ultrasonic, centrifuge, and gas chromatography-mass spectrometry for the detection of these drugs in solid samples. Most of the parameters that affect the extraction step were optimized. Solid samples were placed in a centrifuge tube and extracted with ethyl acetate:acetone (1:1, two cycles), followed by clean-up with Oasis HLB cartridge and derivatization with N, O-bis(trimethylsilyl) trifluoroacetamide (BSTFA). Satisfactory recoveries were obtained ranging from 66 to 130%, depending on the analyte. Precision expressed as RSD (%) (n=3) was less than 20% for all analytes. The LODs and LOQs were in the range of 0.024 to 1.90ngg-1 which allowed to be applied in the analysis solid samples in Msunduzi and Mgeni rivers. In the solid samples analyzed, NSAID concentration ranged from not detected to 221ngg-1.

Determination of non-steroidal anti-inflammatory drugs in water and urine using selective molecular imprinted polymer extraction and liquid chromatography

A selective solid-phase extraction was employed for the improvement of the determination of non-steroidal anti-inflammatory drugs (NSAIDs) in continental water and urine samples. Ketoprofen, naproxen, diclofenac, and ibuprofen were selected as target analytes due to they are the most frequently administered and consumed NSAIDs. These compounds were extracted using molecular imprinted polymers and determined by liquid chromatography with diode array (DAD), and tandem-mass spectrometry (MS–MS) detectors. Performance of DAD and MS–MS detectors was evaluated throughout this study. The obtained limits of quantification, after a 50-fold preconcentration solid-phase extraction, varied from 20 to 30μgL−1 for DAD, and from 0.007 to 0.017μgL−1 for MS–MS for both types of sample matrixes. Quantitative recoveries were found for blank-samples spiked at different NSAIDs concentration levels, ranging from 0.05 to 10mgL−1 for urine and from 0.5 to 500μgL−1 for water. The proposed methodology was applied for the determination of NSAID residues in urine of prescribed individuals, and continental waters.

The evaluation of concentration of certain NSAID in the procedure of screening medicinal and narcotic substances in blood

We have undertaken the metrological assessment of the method for the quantitative determination of a number of non-steroidal anti-inflammatory drugs (NSAID) including ibuprofen, ketorolac, diclofenac, indomethacin, naproxen, and ketoprofen with the use of gas chromatography mass spectrometry in the model blood samples in the framework of the screening survey of medicinal and narcotic substances. The method was evaluated in terms of the following characteristics: specificity, linearity, correctness, precision (reproducibility), and intra-laboratory precision. The proposed method can be applied for the quantitative evaluation of indomethacin, ketoprofen, and naproxen content as well as for the preliminary quantitative determination of ibuprofen and diclofenac in the framework of the chemico-toxicological and forensic chemical analysis. The method can be employed for the quantitative determination of ketorolac from such characteristics as «linearity» and «reproducibility».

Innovative sampling and extraction methods for the determination of nonsteroidal anti-inflammatory drugs in water

Two different innovative approaches were used for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in water: stir bar sorptive extraction (SBSE) and passive sampling, followed by electrospray ionization liquid chromatography–tandem mass spectrometry.SBSE was developed by comparing EG-Silicone and PDMS stir bars and optimizing main parameters to attain high preconcentration. Quantitative analysis was carried out by mass spectrometry in negative ionization mode and multiple reaction monitoring. The SBSE-LC-MS/MS method provided satisfactory figures of merit with LOD (7.5–71ngL−1) and LOQ (22.5–213ngL−1). The developed method was successfully applied to real samples collected from river water and wastewater effluents. The obtained results showed the presence of all analytes at trace levels, in a wide range of concentrations. The passive sampling approach was carried out by using Polar Organic Chemical Integrative Sampler (POCIS); samplers were deployed for 15 days in river and tap water, allowing to detect analytes at ultra-trace levels. Time-Weighted Average concentration of NSAIDs in river water was estimated in the range 0.33–0.46ngL−1, using the sampling rates previously obtained by means of a simple calibration system.

Concentration of non-steroidal anti-inflammatory drugs in the pelvic floor muscles: an experimental comparative rat model.

PurposeThe aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model.Materials and MethodsWe used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma).ResultsDiclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85±0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs.ConclusionDiclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle.

Non-Steroidal Anti-Inflammatory Drugs and Imatinib; Drug Interactions That May Impact Efficacy,

Abstract 3501 Aim:The human organic cation transporter-1 (OCT-1) is the primary active influx protein for imatinib (IM) into target BCR-ABL-positive cells. The functional activity of the OCT-1 protein (OCT-1 activity; OA) is predictive of molecular response and event-free survival in de-novo chronic phase chronic myeloid leukemia (CP-CML) patients. Due to the common use of non-steroidal anti-inflammatory drugs (NSAIDs) among CML patients on IM to treat musculoskeletal pain, it is of particular interest to investigate the impact of NSAIDs on OCT-1 mediated IM uptake. Methods:12 NSAIDs were firstly examined for their impact on OA using the intracellular uptake and retention (IUR) assay and [14-C]-IM. The degree of in vitro kinase inhibition achieved was assessed using p-Crkl in the IC50imatinib assay. Viable cell numbers were determined by trypan blue exclusion method after 72 hours incubation with the co-administration of NSAIDs and IM. NSAIDs concentration was adjusted to median blood levels on standard doses. Results:The majority of NSAIDs (10 of 12) selected did not induce any significant change in OA in CML cell lines. Compared to control cells, increased OA were observed when K562 or KU812 cells were treated with diclofenac (10μM), and this resulted in a concomitant decrease in the IC50imatinib. In keeping with this, after 72 hours co-incubation with IM, diclofenac resulted in a significantly lower viable cell number compared with IM alone. In contrast, ibuprofen (130μM) led to a significant decrease in OA, resulting in an increased IC50imatinib and thus reduced the inhibition of IM on cell growth number (Table 1).Table 1The effect of diclofenac and ibuprofen on the OCT-1 activity, IC50imatinib and viable cell numbers in KU812 and HL60 cellsOCT-1 activity (percentage of vehicle control)IC50imatinib (μM, mean±SEM)viable cell number after 72 hours coincubation with IM (percentage of vehicle control; IM dose: 0.25μM in K562, 0.05μM in KU812)diclofenac (10 μM)ibuprofen (130 μM)no NSAIDsdiclofenac (10 μM)ibuprofen (130 μM)diclofenac (10 μM)ibuprofen (130 μM)K562127%, n=3*48%, n=4**5.7±0.8, n=33.7±0.7, n=3*8.1±0.5, n=3*71.4%, n=3*167%, n=3*KU812122%, n=6*59%, n=6**3.5±0.6, n=32.2±0.4, n=3*6.6±0.8, n=3*64.3%, n=3*145%, n=3*de-novo CP-CML MNC183%, n=50**59%, n=12**1.0±0.1, n=90.7±0.1, n=9*NANANAHealthy donors106%, n=1050%, n=6**NANANANANA*p<0.01,**p<0.001 compared with vehicle controlThe effects of diclofenac and ibuprofen on IM efficacy were then further investigated using primary samples. In keeping with the results observed in cell lines, diclofenac resulted in significant increases in OA, which translated to a significant decrease in IC50imatinib. Ibuprofen induced significant decreases in OA in all patients and healthy donors (Table 1). Conclusion:These finding provide strong evidence for interactions between some NSAIDs and IM which may substantially impact the response of CML patients to IM. While drugs such as diclofenac are likely to have a positive influence on IM efficacy, the findings observed with ibuprofen suggest caution when administrating NSAIDs to CML patients on IM treatment. Disclosures:Hughes:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ARIAD: Honoraria, Membership on an entity's Board of Directors or advisory committees. Osborn:Novartis: Research Funding. White:Novartis Pharmaceuticals: Research Funding; BMS: Research Funding.