S -ketoprofen

Figure 9.9 Microbial biotransformation of (S)-ketoprofen with Streptomyces sp. ATCC 55043...

Hoke et al. [47] recently did a detailed comparison of SFC-MS-MS, EFLC-MS-MS, and HPLC-MS-MS (hexane/2-propanol/trifluoroacetic acid) conditions for thebioanalytical determination ofR and S ketoprofen in human plasma. The optimum chromatographic conditions included 55% methanol/45% CO2 (EFL conditions) with a Chiralpak AD column. The performance parameters (specificity, linearity, sensitivity, accuracy, precision, and ruggedness) for SEC, EELC, and HPLC were found to be comparable. However, the optimized EELC conditions provided the analysis in one-third the amount of time for the LC-MS-MS conditions, which is 10-fold faster than an LC-UV method [48,49],... 

Table 17.3 contains only few examples of where CMPA have been applied for pharmaceutical analysis. The majority of selectors that have been used are different types of cyclodextrines [39,60], but there is also a macrocyclic antibioticum in the list [59]. Guo et al. [59] applied norvancomycin as a CMPA for an assay of (S)-ketoprofen in capsules, the results are displayed in Eigure 17.6B. They... 

The E value represents the ratio of the specificity constants of the enzyme for the two enantiomers of the substrate and allows one to compare directly the selectivity of different enzymes in a reaction [15], In contrast, using the purified CLC form of the enzyme gives an E = 66, which makes it a viable method for obtaining pure S-ketoprofen [16]. 

S)-ketoprofen, 20, is also an important analgesic used to relieve strong-to-mild pain. It is produced by asymmetric hydrogenation followed by oxidation. 

Garcia, M.L. Tost, D. Vitageliu, J. Lopez, S. Carganico, G. Mauleon, D. Bioavailability of S(+)-ketoprofen after oral administration of different mixtures of ketoprofen enantiomers to dogs. J. Clin. Pharmacol. 1998, 38, 22S-26S. 

Tavcar R, Dernovsek MZ, Brosch S. Ketoprofen intoxication dehritrm. J Clin Psychopharmacol 1999 19(l) 95-6. 

Equine Veterinary Journal 27 247-256 Landoni M F, Lees P 1995b Influence of formulation on the pharmacokinetics and bioavallabllity of racemic ketoprofen in horses. Journal of Veterinary Pharmacology and Therapeutics 18 446-450 Landoni M F, Foot R, Frean S et al 1996 Effects of flunixin, tolfenamic acid, fl(-) and S(+) ketoprofen on the response of equine synoviocytes to lipopolysaccharide stimulation. Equine Veterinary Journal 28 468-475... 

Cross-linked crystals of lipase from Candida rugosa (CRL) were applied in the resolution of racemic ketoprofen chloroethyl ester. In batch-wise operation, the half-life of the catalyst was reached after about 18 cycles or, in terms of enzyme consumption, about 5.6 g of enzyme protein were consumed to prepare 1 kg of (S)-ketoprofen. CRL suffers from a low specific activity towards this poorly water-soluble substrate which may explain the high enzyme input [117]. 

Hoke, S.H., 2ndetal., Comparison of packed-column supercritical fluid chromatography -tandem mass spectrometry with liquid chromatography-tandem mass spectrometry for bioanalytical determination of (R)- and (S)-ketoprofen in human plasma following automated 96-well solid-phase extraction, Anal. Chem., 72(17), 4235, 2000. 

LeckerDN, Khan A (1998) Model for inactiveition of oc-amylase in the presence of salts theoretical and experimental studies. Biotechnol Prog 14(4) 621-625 Lee SL, Burt A, Russotti G et al. (1995) Microfiltration of recombinant yeast cells using a rotating disk dynamic filtration system. Biotechnol Bioeng 48(4) 386-400 Lee KW, Bae HA, Shin GS et al. (2006) Purification and catalytic properties of novel enantiose-lective Upase from Acinetobacter sp. ES-1 for hydrolysis of (S)-ketoprofen ethyl ester. Enzyme Microb Technol 38(3 ) 443 48... 

With respect to 2-APA NSAIDs, diseases such as diabetes and obesity [162] have also been shown to alter the inversion process. In addition, other disease states such as renal failure may interfere with the inversion. For example, S-ketoprofen and its acylglucuronide accumulate in end-stage renal failure, which is consistent with amplification of chiral inversion subsequent to futile cycling [120]. 

Lipase- or esterase-catalyzed hydrolytic resolution of ketoprofen esters was usually employed for the preparation of (isolated microorganisms or commercial lipases have been applied for the enantioselective hydrolysis of racemic ketoprofen esters. A commercial enzyme. Lipase OF from Candida rugosa (Meito Sangyo, Japan), was found to be a good biocatalyst for kinetically resolving the 2-chloroethyl ester of ketoprofen (2-(3-benzoylphenyl)propionic acid). ... 

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