Analysis Of Non-steroidal Anti-inflammatory Drugs Research Articles

Rapid confirmatory analysis of non-steroidal anti-inflammatory drugs in bovine milk by rapid resolution liquid chromatography tandem mass spectrometry

A rapid method has been developed to analyse carprofen (CPF), diclofenac (DCF), mefenamic acid (MFN), niflumic acid (NIFLU), naproxen (NAP), oxyphenylbutazone (OXYPHEN), phenylbutazone (PBZ) and suxibuzone (SUXI) residues in bovine milk. Milk samples are extracted with acetonitrile and sample extracts were purified on Evolute™ ABN solid phase extraction cartridges. Aliquots were analysed by rapid resolution liquid chromatography tandem mass spectrometry (RRLC-MS/MS) with a runtime of 6.5 min. The method was validated in bovine milk, according to the criteria defined in Commission Decision 2002/657/EC. CCα values of 0.46, 1.08, 0.92, 1.26, 1.29, 2.12, 0.55 and 2.86 ng mL −1 were determined for CPF, DCF, MFN, NIFLU, NAP, OXYPHEN, PBZ and SUXI, respectively. CCβ values of 0.79, 1.85, 1.56, 2.15, 2.19, 3.62, 0.94 and 4.87 ng mL −1 were determined for CPF, DCF, MFN, NIFLU, NAP, OXYPHEN, PBZ and SUXI, respectively. The measurement uncertainty of the method was estimated at 9, 28, 28, 45, 46, 45, 10 and 39% for CPF, DCF, MFN, NIFLU, NAP, OXYPHEN, PBZ and SUXI. Fortifying bovine milk samples ( n = 18) in three separate assays, show the accuracy of the method to be between 82 and 108%. The precision of the method, expressed as RSD values for the within-lab reproducibility at the three levels of fortification (5, 7.5 and 10 ng mL −1) was less than 16%, respectively. The advantage of the method is that low ng mL −1 levels can be detected and quantitatively confirmed rapidly in milk and that 3 batches of samples can be analysed within a single day using RRLC-MS/MS with a runtime of 6.5 min.

First interlaboratory exercise on non-steroidal anti-inflammatory drugs analysis in environmental samples

Comparability of monitoring data are essential for any meaningful assessment and for the management of environmental risks of emerging pollutants. The reliability and comparability of data at European level is often limited, because analytical methods for emerging pollutants are often not fully validated, not harmonized or not suitable for all relevant matrices. This paper describes a collaborative interlaboratory exercise for the analysis of non-steroidal anti-inflammatory drugs (NSAIDs) residues in freshwater and wastewater, held in the framework of the EU project "Network of reference laboratories for monitoring of emerging environmental pollutants" (NORMAN). The NSAID compounds selected in this study were ketoprofen, naproxen, ibuprofen and diclofenac. Thirteen laboratories distributed along nine European Countries (Austria, France, Germany, Greece, Italy, Slovak Republic, Slovenia, Spain, and Switzerland) took part in this exercise, 126 samples were analyzed and a total number of 473 values in duplicate were collected. Samples selected in this study include environmental water (river water and waste water) and artificial water (fortified environmental and distilled water) with different ranges of complexity. Two analytical methods were proposed by the organiser; one is based on the use of solid phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the second one is based on SPE followed by gas-chromatography-mass spectrometry (GC-MS), however, in the first round some different approaches were also admitted. The main goals of this interlaboratory comparison were to evaluate the available analytical schemes for NSAID analysis in natural waters, to evaluate the repeatability (r) and reproducibility (R) between participating laboratories, and to evaluate the influence of the analytical method and sample matrices on the results.

The Bone and Joint Decade 2000–2010 Task Force on Neck Pain and Its Associated Disorders

Scott Haldeman, DC, MD, PhD,1 Linda Carroll, PhD,2 J. David Cassidy, DC, PhD, DrMedSc,3 Jon Schubert, CMA,4 and Ake Nygren, DDS, MD, DrMedSc5 1Department of Neurology, University of California, Irvine, CA; Department of Epidemiology, School of Public Health, University of California, Los Angeles, CA 2Department of Public Health Sciences, and Alberta Center for Injury Control and Research, School of Public Health, University of Alberta, Canada 3Department of Public Health Sciences, Faculty of Medicine, University of Toronto an Division of Health Outcomes and Research, Toronto Western Research Institute, University Health Network, Toronto, Canada 4CEO–SGI, Regina, Saskatchewan, Canada 5Department of Clinical Sciences, Danderyd Hospital, Division of Rehabilitation Medicine, Karolinska Institutet, Stockholm, Sweden

Automated Analysis of Non-steroidal Anti-inflammatory Drugs in Environmental Water by On-line In-tube Solid-phase Microextraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry

A simple and sensitive method for the simultaneous determination of 15 non-steroidal antiinflammatory drugs (NSAIDs)—acetaminophen, ibuprofen, naproxen, fenoprofen, flurbiprofen, loxoprofen, ketoprofen, mefenamic acid, flufenamic acid, diclofenac, tolfenamic acid, oxaprozin, phenylbutazone, indomethacin, and acemetacin—in environmental water was developed. This method consists of in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC-MS-MS). These NSAIDs were analyzed within 10 min using an ODS-3 column and 5 mM aqueous ammonium formate/acetonitrile (60/40, v/v) as the mobile phase. Electrospray ionization conditions in the negative ion mode were optimized for MS-MS detection of these drugs. The optimum in-tube SPME conditions were 20 draw/eject cycles of 40 μL of sample at a flow rate of 150 μL/min using a Carboxen-1006 PLOT capillary column as an extraction device. The extracted NSAIDs were easily desorbed from the capillary by passage of mobile phase. Using the in-tube SPME/LC-MS-MS method, good linearity of the calibration curve (r≥0.9997) was obtained in the concentration range from 0.1∼10 ng/mL for all compounds examined. The limits of detection (S/N=3) of NSAIDs ranged from 5∼65 pg/mL. This method could be successfully applied to analysis of surface water and wastewater without any other pretreatment or interference peaks. The recoveries of NSAIDs spiked into river water were above 80%, and the relative standard deviations were below 8.3%. Among the NSAIDs tested in this study, loxoprofen was detected in hospital wastewater at 458 pg/mL.

Electrokinetic supercharging for on-line preconcentration of seven non-steroidal anti-inflammatory drugs in water samples

The development of new sensitive methods for the analysis of non-steroidal anti-inflammatory drugs (NSAIDs) in water samples is of great importance. In this work, seven NSAIDs were separated within 9 min using 15 mM sodium tetraborate (pH 9.2) containing 0.1% (w/v) hexadimethrine bromide (HDMB) and 10% (v/v) methanol. Field-amplified sample injection (FASI) was examined and found to improve the detection limits by 200-fold providing detection limits of 0.6–2.0 μg/L, but these are insufficient for the determination of NSAIDs as environmental pollutants in water samples. To improve the sensitivity further, electrokinetic supercharging (EKS) was examined. The optimum EKS method involved hydrodynamic injection leading electrolyte (100 mM NaCl, 30 s, 50 mbar), electrokinetic injection of the sample (200 s, −10 kV) and finally injection of the terminating electrolyte (100 mM 2-(cyclohexylamino) ethanesulphonic acid, CHES, 40 s, 50 mbar). With this method, the sensitivity was improved by 2400-fold giving detection limits of 50–180 ng/L. The developed method was validated and then applied to the analysis of wastewater samples from a local sewage treatment plant. The detection limits were found to increase by approximately 10-fold, however, this is still lower than levels previously found in wastewater samples from European and Mediterranean cities. The proposed method has the advantage of simplicity and achieving sensitivity through high-preconcentration power without the use of off-line chromatographic sample cleanup.

Capillary electrophoresis for the analysis of non-steroidal anti-inflammatory drugs

Thousands of tons of pharmacologically active substances are used annually to treat or to prevent illnesses, or to help people with the stress of modern life. Non-steroidal anti-inflammatory drugs (NSAIDs) are the group most often used in human health care, since they are available without prescription for treatment of fever and minor pain. The present review addresses the use of various modes of capillary electrophoresis (CE) for the analysis of NSAIDs. Special attention is paid to those aspects that decrease the limits of detection of these drugs by using an electrophoretic or a chromatographic approach to preconcentration. We also examine application of CE to the analysis of NSAIDs from pharmaceutical preparations, biological samples and water samples with their sample pre-treatments. Finally, we briefly outline future trends.

Analysis of Nonsteroidal Anti-inflammatory Drugs in Water Samples Using Microemulsion Electrokinetic Capillary Chromatography Under pH-Suppressed Electroosmotic Flow with an On-Column Preconcentration Technique

Microemulsion electrokinetic capillary chromatography (MEEKC) in a suppressed electroosmotic flow (EOF) strategy was investigated for analysing a group of nonsteroidal anti-inflammatory drugs (NSAIDs) in water samples. The EOF was effectively suppressed with an acidic buffer as the aqueous phase. Four water immiscible solvents, oils (n-heptane, n-octane, ethyl acetate and di-n-butyl tartrate) and three organic solvents (methanol, 2-propanol and acetonitrile) were tested to optimise the pseudostationary phase and to obtain efficient separations. The optimum microemulsion background electrolyte (BGE) solution consisted of 0.8% (w/w) n-heptane, 6.6 (w/w) butan-1-ol, 15.0% (w/w) acetonitrile, 3.3% (w/w) sodium dodecyl sulfate (SDS), and 74.3% (w/w) of 25 mM sodium phosphate at pH 2.5. Stacking with reverse migrating pseudostationary phase (SRMP) was applied to enhance the concentration sensitivity of the NSAIDs. When this preconcentration technique was used, the sample stacking and the separation processes took place successively with the same voltage without an intermediate polarity switching step. Detection limits (LODs) in the order of 5–15 µg L−1 for the NSAIDs were obtained using SRMP for standard solutions. The developed method was validated for the analysis of NSAIDs in tap water samples by combining an off-line solid-phase extraction (SPE) step and the on-column preconcentration technique SRMP. The LODs were in the 100–230 ng L−1 range.

TLC analysis of non-steroidal anti-inflammatory drugs and videodensitometric determination of fenbufen in tablets

The chromatographic separation of fenbufen, ibuprofen, ketoprofen, diclofenac sodium, mefenamic acid, and tiaprofenic acid has been investigated. Normal-phase chromatography on silica gel by the ascending and horizontal techniques, and reversed-phase chromatography on octadecyl-bonded silica gel (RP-18) in horizontal chambers, were performed with suitable mobile phases. The substances were identified by UV illumination at λ = 254 nm and by use of dyeing reagents. Reversed phase chromatography with phosphate buffer, pH 5.73–10% CTMA-Br in methanol, 3.5 + 6.5 ( v/v ), as mobile phase enabled better separation of the six drugs than normal-phase mode. A simple videodensitometric TLC method on silica gel RP-18 was developed and validated for quantitative determination of fenbufen in tablets. The limits of detection and quantification were determined by videodensitometry at λ = 254 nm. A calibration plot was constructed in the range 2.0–12.0 μg/5-μL spot and was linear with a good correlation coefficient (0.992...

A Case-Control Analysis of Nonsteroidal Anti-Inflammatory Drugs and Alzheimer’s Disease: Are They Protective?

In many studies of nonsteroidal anti-inflammatory drugs (NSAIDs) and Alzheimer’s disease (AD), the exposure to NSAIDs was concurrent with AD or based on self (or surrogate) report. We conducted a case-control analysis of the Québec participants in the Canadian Study of Health and Aging who received a diagnosis of AD (cases) or were found to be cognitively unimpaired on screening (controls). Information on drug use was obtained from the Québec Provincial Pharmaceutical Services Database. There was no significant difference in the proportion of cases and controls who had received any NSAID prescriptions in the 3 years prior to the onset of symptoms of dementia; amongst NSAID users, there was no difference in mean dose or duration. Our findings, using a measure of drug use prior to symptom onset and not subject to recall bias, do not support a protective effect for NSAIDs.

Development and robustness testing of a nonaqueous capillary electrophoresis method for the analysis of nonsteroidal anti-inflammatory drugs

Nine non steroidal anti-inflammatory drugs were simultaneously separated by nonaqueous capillary electrophoresis with a methanol–acetonitrile (40:60, v/v) mixture containing 20 m M ammonium acetate. The effect of solvent composition, electrolyte nature and concentration on the electrophoretic behavior of the selected drugs was systematically studied. Investigated electrolytes were ammonium, lithium and sodium acetate. Modification of the solvent and/or the electrolyte composition was found to alter the migration order of the pharmaceutical drugs. Finally, to assess method robustness, three sensitive electrophoretic parameters as well as their interactions were evaluated using a full factorial design at two levels.

Meconium Analysis of Nonsteroidal Antiinflammatory Drugs (NSAID) and its Relationship to Persistent Pulmonary Hypertension of the Newborn (PPHN)† 945

Meconium Analysis of Nonsteroidal Antiinflammatory Drugs (NSAID) and its Relationship to Persistent Pulmonary Hypertension of the Newborn (PPHN)† 945

Unusual Analyte Adsorption Effects on Inert Lc Components

Abstract The use of injector loops made of the inert polymer PEEKTM was studied for the analysis of non-steroidal anti-inflammatory drugs (NSAID) using microbore LC with peak compression. Surprisingly it was found that the use of PEEK not only failed to prevent adsorption of analyte in the loop but, in this instance, actually exacerbated the problem. The effect of loop overfill volume, competing NSAID in the sample solution and percentage organic component in the mobile phase on this phenomenon was investigated. Comparison was also made between PEEKTM and other materials used for injector loops.

Detection of flunixin in equine urine using high-performance liquid chromatography with particle beam and atmospheric pressure ionization mass spectrometry after solid-phase extraction.

A normal-phase HPLC method combined with particle-beam mass spectrometry (PB-MS) was developed for the analysis of non-steroidal anti-inflammatory drugs (NSAIDs). The forty one NSAIDs analysed responded in one or more (electron impact, positive and negative chemical ionisation) modes and highly characteristic spectra were produced. A mixed-mode solid-phase extraction (SPE) method for isolating acidic NSAIDs was developed using the Bond Elut Certify II cartridge. The average recovery was 88.5%. Flunixin, extracted by SPE from urine of a mare to which the meglumine salt had been administered was positively identified by HPLC-PB-MS and HPLC-atmospheric pressure ionization (API) MS methods.

Quantitative analysis of non-steroidal anti-inflammatory drugs by capillary zone electrophoresis

The potential utility of capillary zone electrophoresis (CZE) for the separation and quantitative determination of some non-steroidal anti-inflammatory drugs (NSAIDs) was investigated. The influence of different parameters on migration times, peak symmetry, efficiency and resolution was studied; these parameters included the nature and concentration of the anionic and cationic components of the separation buffer. A buffer consisting of 75 mM glycine adjusted to pH 9.1 with triethanolamine was found to provide a very efficient and stable electrophoretic system for the CZE analysis of NSAIDs, giving RSD values of about 0.1 and 0.5% for the within-day reproducibility of migration times and peak areas, respectively at a concentration of 25 μg ml −1 ( n = 5). Response was linear from 2–100 μg ml −1 for both sulindac and tiaprofenic acid, for which the LOO values were 2.8 and 1.9 μg ml −1, respectively, using UV detection at 280 nm. Accuracy for each drug was 102–103%.

Rapid high-performance liquid chromatographic assay for the simultaneous analysis of non-steroidal antiinflammatory drugs in plasma

A high-performance liquid chromatographic assay has been developed for the determination of a number of non-steroidal anti-inflammatory drugs in plasma. The samples were prepared by adding acetonitrile and perchloric acid to 200 μl of plasma. Diclofenac, fenoprofen, ketoprofen, naproxen, phenylbutazone, piroxicam and sulindac were quantified in the supernatant produced using a mobile phase of phosphoric acid 0.03% (pH 2.5) -acetonitrile and a detecting wavelength of 254 nm. The reproducibility, linearity, precision and specificity of the assay were determined and found to be satisfactory. Alteration of the detection wavelength to 229 nm also permitted accurate determination of ibuprofen concentration in plasma. While reduction of the organic solvent content of the mobile phase and alteration of wavelength to 313 nm produced a system capable of quantizing salicylate and its metabolites in plasma and by further reducing the detecting wavelength to 237 nm, aspirin also was quantifiable. These methods have been applied in a cross-sectional study of medication compliance among rheumatoid arthritis patients treated with non-steroidal anti-inflammatory drugs.