Cellulose-based phase

Online detection using 4H nuclear magnetic resonance (NMR) is a detection mode that has become increasingly practical. In a recent application, cell culture supernatant was monitored on-line with 1-dimensional NMR for trehalose, P-D-pyranose, P-D-furanose, succinate, acetate and uridine.33 In stopped-flow mode, column fractions can also be analyzed by 2-D NMR. Reaction products of the preparation of the neuromuscular blocking compound atracurium besylate were separated on chiral HPLC and detected by 4H NMR.34 Ten isomeric peaks were separated on a cellulose-based phase and identified by online NMR in stopped-flow mode. 

Advances in preparative enantioseparation by simulated moving bed (SMB) chromatography have occurred in the last 10 years. SMB was invented in the 1960s and was used by the petrochemical and sugar industries. Now with the improvements in stationary phases and hardware it is an option for the large-scale preparation of enantiomerically pure material. The majority of the latest published data are using either amylose- or cellulose-based phases because of their selectivity. There are now examples in the literature of the commercial separation on the multi-ton scale.8... 

M. Tanaka and H. Yamazaki, Dkect detemination of pantoprazole enantiomers in human serum by reversed-phase liigh peifomance liquid chi omatography using a cellulose-based cliiral stationaiy phase and column-switching system as a sample cleanup procedure , Aim/. Chem. 68 1513-1516(1996). 

The TLC process is an off-line process. A number of samples are chromatographed simultaneously, side-by-side. HPTLC is fast (5 min), allows simultaneous separation and can be carried out with the same carrier materials as HPLC. Silica gel and chemically bonded silica gel sorbents are used predominantly in HPTLC other stationary phases are cellulose-based [393]. Separation mechanisms are either NPC (normal-phase chromatography), RPC (reversed-phase chromatography) or IEC (ion-exchange chromatography). RPC on hydrophobic layers is not as widely used in TLC as it is in column chromatography. The resolution capabilities of TLC using silica gel absorbent as compared to C S reversed-phase absorbent have been compared for 18 commercially available plasticisers, and 52 amine and 36 phenolic AOs [394]. 

Carbon fibers, 4 735 24 624 26 729-749 applications of, 26 745 cellulose-based, 26 735-736 crystallite dimensions in, 26 737-739 gas-phase grown, 26 736-737 PAN-based, 26 730-733 pitch-based, 26 733-735 plasma-treated, 26 744 processing of, 26 730-737 properties of, 26 739-743 prospects for, 26 746-747 quality control and specifications for, 26 745-746... 

This method is very useful for separating amino acids found in food samples. The most effective matrix for separation is an absorbent cellulose-based filter paper. A very effective mobile phase is 70% isopropyl alcohol in water. Although the 20 amino acids are chemically very similar, they may be successfully separated by this method. Amino acids interact with the stationary phase to different extents, thus moving at different speeds. Chemical differences among amino acids that determine migration speed include molecular weight, charge, and polarity. 

Particular examples for the separation of optical isomers in the (pharmaceutical) industry include prazinquatel [51], 3-blockers [52], chiral epoxide [6],thia-diazin EMD5398 [18] and hetrazipine [7]. The Belgian company UCB Pharma uses a large-scale SMB from NOVASEP to perform optical isomer separation at a scale of several tons per year. Almost all of these separations are performed on cellulose-based stationary phases using organic eluents [4]. 

Based on the high peak capacity of CE, the separation speed, and the availability of numerous chiral selectors and the simplicity of the systems, chiral CE is superior to chiral HPLC separations. This is as well reflected by the high number of publications on chiral CE in recent years. Chiral HPLC is suffering from low peak capacity (broad peaks), system stability (often normal phase systems), pressure sensitivity of columns (often cellulose-based column materials), and as a consequence long separation times. 

Organic polymers and resins have also been used for zeolite binding. An early example is the use polyurethane in the formahon of vibration-resistant zeolite porous bodies for refrigerant drying [90]. Organic binders such as cellulose acetate and other cellulose-based polymers have also used to mitigate problems with binder dissolution in aqueous phase separations [91, 92]. Latex has also been used as a water-stable organic binder [93]. More recently, thermoplastic resins, such as polyethylene have also been used as binders for zeolites [94]. 

L. Miller and R. Bergeron, Analytical and preparative resolution of enantiomers of verapamil and norverapamil using a cellulose-based chiral stationary phase in the reversed-phase mode, J. Chromatogr., 648 36(1993)... 

Chiral separations have become of significant importance because the optical isomer of an active component can be considered an impurity. Optical isomers can have potentially different therapeutic or toxicological activities. The pharmaceutical literature is trying to address the issues pertaining to these compounds (155). Frequendy separations can be accomplished by glc, hplc, or ce. For example, separation of R(+) and S(—) pindolol was accomplished on a reversed-phase cellulose-based chiral column with fluorescence emission (156). The limits of detection were 1.2 ng/mL of R(+) and 4.3 ng/mL of 5/—) pindolol in serum, and 21 and 76 ng/mL in urine, respectively. 

The substrate, 4-(6-methoxy-2-benzoxazolyl)acetophenone, the R and S enantiomers of the product, 4-(6-methoxy-2-benzoxazolyl)phenethyl alcohol, and the internal standard, 3-acetyl-7-(dimethylamino)coumarin, were separated by chromatography on a cellulose-based chiral column (Chiracel OD from Daicel). The mobile phase was a 93 7 mixture (v/v) of n-hexane and 2-propanol, which was used at ambient temperature and a flow rate of 1.2 mL/ min. Detection of the enantiomeric alcohols and the internal standard was by fluorescence, with excitation and emission wavelengths of 315 and 375 nm, respectively. 

Hollow membrane fibers are required for many medical application, e.g. for disposable dialysis. Such fibers are made by usmg an appropriate fiber spinning technique with a special inlet in the center of the spinneret through which the fiber core forming medium (liquid or gas) is injected. The membrane material may be made by melt-spinning, chemical activated spinning or phase separation. The thin wall (15-500 xm thickness) acts as a semi-permeable membrane. Commonly, such fibers are made of cellulose-based membrane materials such as cellulose nitrate, or polyacrylonitrile, polymethylmethacrylate, polyamide and polypropylene (van Stone, 1985). 

T. Loughlin, R. Thompson, G. Bicker, R Tway, and N. Grinberg, Use of subcritical fluid chromatography for the separation of enantiomers using packed column cellulose based stationary phase. Chirality 8 (1996), 157. 

Artefacts that arise from gas in the stomach and adjacent bowel often limit the diagnostic accuracy of abdominal ultrasound. Research to overcome this problem has focused on cellulose-based suspensions. An agent has been developed based on simethicone-coated cellulose— SonoRx (Bracco Diagnostics, Princeton, NJ), which displaces and disperses gas bubbles. In a phase 2 chnical study, 93 patients underwent upper abdominal sonography before and after a randomized dose of the contrast agent (200, 400, 600, 800, or 1000 ml) (15). Anatomical visualization was improved as follows the stomach in 82% of patients, the duodenum in 63%, the pancreatic head and body in 61%, and the pancreatic tail in 67%. There were 14 adverse events in 11 patients and only five were considered to be related to the contrast agent. The main adverse effects were mild diarrhea and nausea. 

The enantiomeric purity of 2-arylpropionic acids used as pharmaceuticals was determined after derivatizing to the corresponding amides with various PAA and HAA. End analysis was by HPLC-UVD, with simultaneous measurement at 230 and 254 nm, using a cellulose-based stationary phase. The best derivative for routine determinations was chosen in each case after establishing the chromatographic parameters of the enantiomeric pair of derivatives197. 

From the list in Table 3.9, cellulose and amylose-based phases are by far the most often used in preparative and, especially, SMB applications. These adsorbents offer good productivities because of their high loadabilities (Fig. 3.22). In addition, the four most commonly used CSP of this type separate a broad range of different race-mates. The major problem of these adsorbents is their limited solvent stability, especially towards medium-polar solvents such as acetone, ethyl acetate or dioxane. In the past their use in conjunction with aqueous mobile phases was not recommended by the manufacturer as well. However, this limitation was successfully overcome by recent studies, in which amylose- and cellulose-based CSPs are transferred to the reversed phase (RP) mode with aqueous mobile phases. The first results for the use of polysaccharide-type phases with aqueous solvents were reported by Ishikawa and Shibata (1993) and McCarthy (1994). The stability of the adsorbent after switching to RP conditions has been reported by Kummer et al. (1996) to be at least 11 months and by Ning (1998) to be 3 years. No peak deviation is observed after switching to RP mode. Novel developments have led to polysaccharide-based adsorbents dedicated to use with nearly all organic solvents (Cox and Amoss, 2004). 

With chromatographic production processes the elution order of the enantiomers is of importance. In SMB processes the raffinate enantiomer can often be obtained with better economics as it is recovered at higher purities and concentrations. If the CSP offers the possibility of choosing one of the two optically active forms of the selector, the adsorbent on which the desired enantiomer elutes first should be chosen. This option can be used especially with the brush-type phases with monomolec-ular chiral selectors. Even if the CSP is not available in both forms, the elution order should be checked carefully as the elution order might be reversed on two very similar adsorbents or with two similar mobile phase combinations. Okamoto (1991) and Dingenen (1994) have shown that by changing only from 1-propanol to 2-propanol, respectively with 1-butanol, the elution order on a cellulose-based CSP might reverse. 

Okamoto, M., Nalcazawa, H., Reversal of elution order during direct enantiomeric separation of pyriproxyfen on a cellulose-based chiral stationary phase,/. Chromatogr., 1991, 588, 177-180. 

In a few cases, the option of preparing tailor-made CSPs for a particular racemic structure has been applied. For example, we prepared on an empirical basis a particular polysaccharide-based CSP for the separation of the enantiomers of the enantiomers of the LTD4 antagonist iralukast and of the antimalaria agent benflumethol [87]. These two racemic drugs were only poorly resolved on the commercially available polysacharide-based phases whereas an excellent separation was obtained on the carbamate derivative of cellulose obtained from cellulose and 3-chloro-4-methylphe-nylisocyanate. The prepared CSP was also used to perform pharmacokinetic studies. 

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