Nonsteroidal anti-inflammatory drugs separation

Chcrkaoui and Veuthey have used nonaqueous CE for the simultaneous separation of nine nonsteroidal anti-inflammatory drugs. Separation was achieved using methanol/acetonitrile (40/60 v/v) with 20 mM ammonium acetate. Perhaps more important, the elution order of the individual components was shown to change with both solvent and electrolyte composition, indicating that selectivity can be manipulated. 

A number of drugs have been successfully separated using MIPs. Naproxen , (S)-6-methoxy-a-methyl-2-naphthaleneacetic acid, is a nonsteroidal anti-inflammatory drug (NSAID) that is administered as the S enantiomer. Naproxen (structure 16.20) will be used to illustrate the MIP sequence. Naproxen has both polar and nonpolar domains. It also has a fused-ring aromatic site. 

Lelievre and Gareil (31) studied chiral separations of nonsteroidal anti-inflammatory drugs (carprofen, flurbiprofen, indoprofen, ketoprofen, naproxen, propafenone, and suprofen) and determined the acidity and inclusion complex formation constants of these chiral compounds with different neutral CDs (/3-CD, HP-/3-CD, DM-/3-CD, TM-/3-CD, and HP-y-CD). In... 

The SFC separation of nonsteroidal anti-inflammatory drugs (NSAIDs) was investigated by Jagota and Stewart [6]. These compounds vary in chemical structure and functional group chemistry and provide a representative sample of acidic drugs to study. Using a 10-m x 50-fim ID... 

Figure 4 Nonsteroidal anti-inflammatory drugs, acetaminophen, and caffeine separated by CEC on a 75-mm-i.d. column packed with 5-mm ODS Nucleosil particles immobilized within a polymer matrix. Mobile phase 70% acetonitrile/30% acetate, 10 mM (pH 3.0). UV detection at 254 and 220 nm 20 kV applied, effective length 17 cm, total length 26 cm. Analytes (1) unknown impurity (2) acetaminophen (3) caffeine (4) aspirin (5) naproxen (6) flurbiprofen (7) ibuprofen. (Reprinted from Ref. 22, with permission.)...

The separation of nonsteroidal anti-inflammatory drugs (NSAIDs) has recently attracted considerable interest. Nonsteroidal anti-inflammatory drugs are agents that, in addition to having anti-inflammatory action, also have analgesic, antipyretic, and platelet-inhibitory properties. They are used primarily in the treatment of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation. 

Figure 29 Separation of the nonsteroidal anti-inflammatory drugs ibuprofen (peak 1), naproxen (2), ketoprofen (3), and suprofen (4) in anion-exchange CEC mode using a strong anion-exchange monolithic column. Conditions on-column alkylated monolith prepared from mixtures consisting of 8% 2-dimethylaminoethyl methacrylate, 24% 2-hydroxyethyl methacrylate, 8% ethylene dimethacrylate, 20% cyclohexanol, 40% 1-dodecanol UV-initiated polymerization at room temperature for 16 h cfpmode= 1423 nm. Column dimensions inner diameter 0.1 mm, total length 335 mm, effective length 250 mm. Mobile phase 0.4 mol/L acetic acid and 4 mmol/L triethylamine in acetonitrile/methanol (60/40), voltage -25 kV, injection -5 kV for 5 s, temperature 50°C, UV detection at 250 nm. (Reprinted from Ref. 127, with permission.)...

On a more rational basis (concept of reciprocity), Pirkle and Welch also developed a particular CSP for the separation of the enantiomers of the analgesic agent naproxen and other nonsteroidal anti-inflammatory drugs (NSAID) [88]. It appeared later that this CSP had a relatively broad application range [89]. 

Phylloquinone, menaquinone, and menaphthone have been extracted from serum into supercritical CO2 and separated with SFC, with detection at 250 nm (127). Serum, supported on celite, was transferred to extraction cartridges and extracted with supercritical CO2 at 45°C prior to the analysis of benzodiazepines, anabolic agents, and nonsteroidal anti-inflammatory drugs by HPLC (128). Phenobarbital, butalbital, pentobarbital, and thiopental have been extracted from human serum prior to liquid chromatography-negative-ion electrospray tandem mass spectrometry analysis (129). The sample was extracted with supercritical CO2 at 40°C and 507 bar with static extraction for 5 min followed by dynamic extraction for 30 min. Calibrations graphs were linear for 1-60 pg/mL of each barbiturate and the detection limits were 23, 25, 50, and 225 ng/mL of thiopental, pentobarbital, butalbital, and phenobarbital, respectively. In the determination of the cited analytes in serum spiked at the 10- and 50-pg/mL levels, the recoveries were 94.2-106.9% and the RSDs were 1.14-5.18% (three replicates). 

A.2.3. Example of an Applied Response Surface Design. In the optimization phase of the development of a CE method for the chiral enantio-separation of a nonsteroidal anti-inflammatory drug (28), a circumscribed CCD was performed. The applied symmetrical response surface design is as shown in Table 2.14, with a = 2 f = 1.68. The center point (experiment 15 in Table 2.14) was replicated five times (experiments 15-19). 

M Fillet, I Bechet, V Piette, J Crommen. Separation of nonsteroidal anti-inflammatory drugs by capillary electrophoresis using nonaqueous electrolytes. Electrophoresis 20 1907-1915, 1999. 

De Rossi, A. and Desiderio, C., Separation of negatively charged nonsteroidal anti-inflammatory drugs by reversed-phase capillary electrochromatography, J. Chromatogr. A, 984, 283, 2003. 

Ibuprofen, (a-methyl-4-(2-methylpropyl)benzene-acetic acid), is a well known proprietary nonsteroidal anti-inflammatory drug used to reduce pain, fever and inflammation, particularly in arthritis. The drug exists as two enantiomers and has been successfully separated by liquid chromatography using Chirobiotic V (Vancomycin). 

The most extensive studies on molecular-imprinted polymers as stationary phases for enantioseparations were conducted using amino acids and their derivatives as the template, but many other classes of compounds have been studied, including peptides, p-blockers, and nonsteroidal anti-inflammatory drugs (see Table 3). Examples of separations are reported in Figs. 6-8. 

A pioneering work on the multi-step flow chemistry is the continuous synthesis of ibuprofen, a h h-volume, nonsteroidal anti-inflammatory drug. The assembly of the three-step synthesis into one continuous system was envisioned. The researchers first optimized the three reactions separately and then assembled the three steps into a single continuous system. The synthesis of ibuprofen was however seen as an entity, instead of a series of independent reactions. In the design of each reaction, it was taken into account that the synthesized byproducts and excess reagents would not interfere in the subsequent reactions, which eventually eliminated the need for purification and isolation steps. The Friedel—Crafts acylation. 

A variety of pharmaceutical drugs or intermediates, such as -blockers, P-agonists, benzodiazepines, nonsteroidal anti-inflammatory drugs, and sulfoxides, can be enantioresolved on the same polysaccharide CSP in all HPLC separation modes and in SFC. A common structural feature of these compounds is that they all contain at least one aromatic group and multiple hydrogen-binding sites in... 

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