Benoxaprofen enantiomers

Balenine, 180 Barban, 107 Barbitals, 196 Barbiturates, 186 Basic Green, 121 Basic Violet, 121 Basic Yellow, 122 Baycaib (Fenobucarb), 360 Beauveticin, 400 Beclomethasone, 215, 515 Bellidifolin-8-O-glucoside, 408 Benazolin, 109 Bendroflumethiazide, 549 Benomyl, 357, 371 Benoxaprofen enantiomers Benoximate, 532 Benperidol, 518 Bentazone, 106,109 Benz[/)aceanthtylene metabolites, 99 Benz[a]acridine, 228, 294 Benz[c]acridine and subs analogs, 231 Benzaldehyde, 86, 91, 293, 337, 342, 383, 464... 

The conjugates of arylpropionic acids enantiomers with D-glucuronic add were separated on a Beckman Ultrasphere ODS column (4.6 mm x 250 mm, 5 / m) column. The mobile phase was a 28 72 (v/v) mixture of acetonitrile and 8 mM tetrabutylammonium hydrogen sulfate buffer (pH 2.5). Five minutes after the diastereomeric conjugates had been resolved, the percentage of acetonitrile was increased to 60% to wash out excess substrate. The mode of detection depended on the samples injected. Fluorescence was used for flunoxaprofen (excitation, 305 nm emission, 355 nm), benoxaprofen (313/ 365 nm) carprofen (285/350 nm), and idoprofen (275/433 nm). UV absorption was used to detect flurbiprofen (255 nm), naproxen (285 nm), ketoprofen (255 nm), pirprofen (265 nm), and cicloprofen (238 nm). 

An interesting fluorescent CDA was developed by Weber et al. (66). These workers converted racemic benoxaprofen, [13], to the corresponding N- R)-ot-methylbenzylamide diastereomers, which were preparatively separated on silica gel LC columns. The separated diastereomers were acid-hydrolyzed to retrieve the individual enantiomers of benoxaprofen. Either enantiomer could then serve as CDA for the resolution and determination of chiral amines. The diastereomeric derivatives of several amines were highly fluorescent and well resolved on silica gel columns or by TLC. One disadvantage of the procedure was that the CDAs had slightly less than 100% enantiomeric purity. 

It is assumed that the coenzyme A ester (CoA-ester) of the R(-)-enantiomer acts as a substrate for the fatty acid deshydrogenase, thus eliminating the chiral center. The next step may, or may not, take place, depending whether or not the CoA-ester must be transferred to an acyl-carrier protein or another site in the fatty acid synthetase system, so that a stereoselective reduction by an enoykeductase can take place. Thus the nature of X is unknown. Similar epimerization reactions were also described for some other arylpropionic acids such as benoxaprofen, carprofen, and isopropyl-indanyl-propionic acid. ° It was demonstrated that the configural inversion does not take place in the liver, and that the responsible enzyme, R-(-)-aryIpro-... 

Clinically this bioinversion process does not occur appreciably with tiaprofenic acid, indoprofen, carprofen, or flurbiprofen, but it does occur substantially for fenoprofen and ibuprofen, for which 100% and 60% of the R-enantiomer is inverted, respectively [32-34]. Bioinversion also occurs for benoxaprofen, an NSAID withdrawn from the market, and it may also occurs for loxoprofen, suprofen, and CS-670, all 2-APA NSAIDs primarily utilized clinically throughout Asia [34-37]. 

There is some evidence that enantiomer intereonversion with some NSAIDs occur predominantly in the GI tract. For example with benoxaprofen, the R to S eonversion, based on enantiomer AUC measurement, occurs more after oral administration than after intravenous (i.v.) or intraperitoneal (i.p.) administration in rats [34], indicating the importance of the GI tract in this conversion. With ketoprofen in rats, the R/S AUC ratio is similar after i.v. and i.p. administration and is about three times lower eompared to this ratio obtained after oral administration, suggesting the importanee of the GI tract in the enantiomer intereonversion [35,36]. 

Enantiomers of six NSAIDs (ibuprofen, pirprofen, ketoprofen, benoxaprofen, carprofen, protizinic acid) were resolved as their ben lamine derivatives on a Chiralcel OJ column ( = 230nm) using an 80/20/0.5 hexane/IPA/acetic acid mobile phase [729]. A 20 pL injection of 500 pg/mL standard was used in the study. Elution was complete in <30 min while obtaining good resolution and good peak shapes. 

The following chiral reagents were employed for diastereomer formation before sample application and chromatography on silica gel or silica gel G TLC plates (L)-leucine Af-carboxyanhydride for D,L-dopa-carboxyl- " C separated with ethyl acetate/formic acid/water (60 5 35) mobile phase and detected by ninhydrin [7 f 0.38 (d)/0.56 (l)] [43] Af-trifluoroacetyl-L-prolyl chloride for D,L-amphetamine separated with chloroform/methanol (197 3) and detected by sulfuric acid/formaldehyde (10 1) (Rf 0.49 (d)/0.55 (l)) [44] Af-benzyloxycarbonyl-L-prolyl chloride for D,L-methamphetamine separated with n-hexane/ethyl acetate/acetonitrile/diisopropyl ether (2 2 2 1) and detected by sulfuric acid/formaldehyde (10 1) [/ f 0.57 (l)/0.61 (d)] [44] (l/ ,2/ )-(-)-l-(4-nitrophenyl)-2-amino-1,3-propanediol (levobase) and its enantiomer dextrobase for chiral carboxylic acids separated with chloroform/ethanol/acetic acid (9 1 0.5) and detected under UV (254 nm) light R[ values 0.63 and 0.53 for 5- and / -naproxen, respectively) [45] (5)-(4-)-a-methoxyphenylacetic acid for R,S-ethyl-4-(dimethylamino)-3-hydroxybutanoate (carnitine precursor) with diethyl ether mobile phase [/ f 0.55 R)/0J9 (5)] [46] and (5)-(4-)-benoxaprofen chloride with toluene/acetone (100 10, ammonia atmosphere) mobile phase and fluorescence visualization (Zeiss KM 3 densitometer 313 nm excitation, 365 nm emission) (respective R values of R- and 5-isomers of metoprolol, oxprenolol, and propranolol were 0.24/0.28, 0.32/0.38, and 0.32/0.39) [47]. 

Enantiomers of metoprolol were determined in urine after the extraction with toluene at pH 9.9 and derivatization with 5 -(+)-benoxaprofen chloride [18]. 

A method for rapid determination of the enantiomers of propranolol after extraction from urine samples at pH 9.9 using toluene was developed. Enantiomers were determined after derivatization with -(-D-benoxaprofen chloride [18]. The established determination conditions are described in Section 14.2.3.3. 

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