Ibuprofen separation

We theorize that the broadness of the second peak in the ibuprofen separation is due to the higher concentration of that enantiomer in the injection mixture. Further tests are being performed to optimize the solvent mixture for this separation, which should also help to reduce the broadness of this peak... 

Numerical Values of A/ita Estimated for Enantiomers of Ibuprofen Separated in Impregnated Silica Gel Plates... 

AGP columns have wide appHcation for the direct separation of enantiomers of many different classes of dmgs, amines, acids, and nonprotolytic compounds (18,23). Acidic dmgs resolved include ibuprofen [15687-27-17, C 2H g02, ketoprofen [22071 -15 ] and naproxen [22204-53-17,... 

Most of the chiral membrane-assisted applications can be considered as a modality of liquid-liquid extraction, and will be discussed in the next section. However, it is worth mentioning here a device developed by Keurentjes et al., in which two miscible chiral liquids with opposing enantiomers of the chiral selector flow counter-currently through a column, separated by a nonmiscible liquid membrane [179]. In this case the selector molecules are located out of the liquid membrane and both enantiomers are needed. The system allows recovery of the two enantiomers of the racemic mixture to be separated. Thus, using dihexyltartrate and poly(lactic acid), the authors described the resolution of different drugs, such as norephedrine, salbu-tamol, terbutaline, ibuprofen or propranolol. 

Fig. 7-19. Enzymatic resolution and separation of ibuprofen sulphonmethyl ester.

In this case study, an enzymatic hydrolysis reaction, the racemic ibuprofen ester, i.e. (R)-and (S)-ibuprofen esters in equimolar mixture, undergoes a kinetic resolution in a biphasic enzymatic membrane reactor (EMR). In kinetic resolution, the two enantiomers react at different rates lipase originated from Candida rugosa shows a greater stereopreference towards the (S)-enantiomer. The membrane module consisted of multiple bundles of polymeric hydrophilic hollow fibre. The membrane separated the two immiscible phases, i.e. organic in the shell side and aqueous in the lumen. Racemic substrate in the organic phase reacted with immobilised enzyme on the membrane where the hydrolysis reaction took place, and the product (S)-ibuprofen acid was extracted into the aqueous phase. 

Figure 11 Separation of anti-inflammatories by CZE at various pHs in a 40-cm polyacrylamide-coated (left) and a 70-cm uncoated (right) capillary Experimental conditions 275 V/cm UV = 215 nm buffers 20 mM borate-100 mM boric acid, pH 8.4 (46 pA) 30 mM phosphate-9 mM borate, pH 7.0 (70 pA) 80 mM MES-30 mM Tris, pH 6.1 (20 pA) peak identification 1 = naproxen, 2 = ibuprofen, 3 = tolmetin. (From Wainwright, A., /. Microcol Sep., 2, 166, 1990. With permission.)...

The International Centre for Diffraction Data (ICDD, Newtown Square, Pa.) maintains a collection of single-phase x-ray powder patterns [5]. There are separate listings of inorganic and organic compounds. The x-ray diffraction data of ibuprofen, as a representative example, is given here (Fig. 1). 

Kwakman et al. [65] described the synthesis of a new dansyl derivative for carboxylic acids. The label, N- (bromoacetyl)-A -[5-(dimethylamino)naphthalene-l-sulfonyl]-piperazine, reacted with both aliphatic and aromatic carboxylic acids in less than 30 min. Excess reagent was converted to a relatively polar compound and subsequently separated from the derivatives on a silica cartridge. A separation of carboxylic acid enantiomers was performed after labeling with either of three chiral labels and the applicability of the method was demonstrated by determinations of racemic ibuprofen in rat plasma and human urine [66], Other examples of labels used to derivatize carboxylic acids are 3-aminoperylene [67], various coumarin compounds [68], 9-anthracenemethanol [69], 6,7-dimethoxy-l-methyl-2(lH)-quinoxalinone-3-propionylcarboxylic acid hydrazide (quinoxalinone) [70], and a quinolizinocoumarin derivative termed Lumarin 4 [71],... 

The structures of luminol derivatives used for HPLC-CL detection are shown in Figure 7A. Analytes labeled with luminol derivatives can be detected using hydrogen peroxide and potassium hexacyanoferrate(III) under alkaline conditions after HPLC separation (Table 1). For example, ibuprofen in saliva [34], saturated... 

Since the separated enantiomers of a dissymmetric compound must crystallize in a different space group than does the racemic mixture, it should not be unanticipated that quantitative XRPD would be useful in the determination of enantiomeric composition. For instance, the differing XRPD characteristics of (S)-(+)-ibuprofen relative to the (-RS)-racemate have been exploited to develop a sound method for the determination of the enantiomeric purity of ibuprofen samples [53]. 

Non steroidal antiinflammatory drugs were among the first classes of chiral compounds investigated in the early stages of the application of macrocyclic antibiotics as chiral selectors therefore, they were screened on vancomycin [7], teicoplanin [30], ristocetin A [33] CSPs under RPmode systems, and on avoparcin CSP under NP mode systems [37]. The enantioresolution of a variety of pro fens was later reported on commercially available vancomycin CSPs [128, 168], and recently on a ME-TAG CSP [58]. Ibuprofen enantiomers were also separated on a CDP-1-containing CSP [55]. Glycopeptide A-40,926 CSP was successfully employed in the analytical and semipreparative separation of 2-arylpropionic acids [63]. 

Rawjee, Y.Y., Stark, D.U., Vigh, G. Capillary electrophoretic chiral separations with cyclodextrin additives I. acids Chiral selectivity as a function of pH and the concentration of P-cyclodextrin for fenoprofen and ibuprofen. J. Chromatogr. 1993, 635, 291-306. 

Stubberud Persson, K., and Astrom, O. (1998). Separation of ibuprofen, codeine phosphate, their... 

In reference 68, a different approach was used to verify the robustness of a CE separation of ibuprofen, codeine phosphate, degradation products, and impurities in a drug product (tablet). Small variations around the optimal conditions obtained during method optimization were introduced and the results were predicted from the response model. The variations in the factor levels during the robustness evaluation were smaller than those evaluated during method optimization. Since both migration times and resolutions were acceptably predicted, the method was considered robust with respect to the small changes. The examined factors... 

Persson Stubberud, K., and Astrom, O. (1998). Separation of ibuprofen, codeine phosphate, their degradation products and impurities by capillary electrophoresis I. Method development and optimization with fractional factorial design. ]. Chromatogr. A 798, 307—314. 

An MEKC method for the determination of ibuprofen, codeine phosphate hemihydrate, their nine potential degradation products, and impurities in a commercial tablet formulation was developed, optimized, and fully validated according to ICH guidelines and submitted to the regulatory authorities. The optimized system containing ACN as organic modifier allowed baseline separation of ibuprofen, codeine, and nine related substances within 12 min. 

In a comparable system, (I ,S)-ibuprofen can be separated by a membrane reactor [83], see Fig. 13.10. The technique comprises a stereo-specific hydrolysis by an enzyme. Subsequently, the enantiomeric ester is extracted into the organic phase on the other side of the membrane. In the system developed by Sepracor Inc., (i )-ibuprofen is selectively hydrolyzed by proteases in a hollow-fiber unit and the (S)-ibuprofen ester can be isolated at 100% yield. This configuration also applies for enantioseparation of other acids such as naproxen and 2-chloropropionic acid. 

JC Reijenga, BA Ingelse, FM Everaerts. Thermodydnamics of chiral selectivity in capillary electrophoresis separation of ibuprofen enantiomers with (3-cyclodextrin. J Chromatogr A 792 371-378, 1997. 

YY Rawjee, RL Williams, G Vigh. Capillary electrophoretic chiral separations using cyclodextrin additives. 3. Peak resolution surfaces for ibuprofen and homatropine as a function of the pH and the concentration of /3-cyclodextrin. J Chromatogr A 680 599-607, 1994. 

In one of the earlier papers, Sun et al. (48) estimated the binding constants of ibuprofen, flurbiprofen, and ketoprofen to HSA and BSA using the mobility-shift mode of ACE. In this case the drugs were actually used as additives to the background buffer to improve the separation of albumin proteins. This is the opposite approach to what is presented in the next... 

For example, in a general screen for acidic drugs, which includes most of the NSAIDs (Fig. 13.5), three mobile phases may be used. Table 13.3 shows the Rf values obtained for three NSAIDs in three different mobile phases. It can be seen from the data in Table 13.3 that even for closely related structures slight differences in polarity and lipophilicity can be exploited to produce separation. For instance, ibuprofen is the least polar drug in system 1 but is the most polar drug in system 3, where the carboxyl groups in the structures will be ionised due to the ammonia in the mobile phase. It can also be seen that the polarity of a mobile phase containing a mixture of chloroform and acetone is similar to that of pure ethyl acetate. 

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