Abstract:The difference in tissue distribution of Ketorolac and its enantiomers were investigated in wistar rats. Separate high performance liquid chromatographic method was developed and validated for determination of Ketorolac and its enantiomers. Oyster BDS (150 × 4.6 mm id., 5 μm particle size) column was used for determination of concentration of Ketorolac. Ketorolac enantiomers were determined using Chiral-AGP column (100 × 4.0 mm I.D., particle size 5 μ, Chrom tech Ltd, Sweden). Detection was done at wavelength … Show more
“…A-Gln was approved in clinical use about 50 years ago, but the techniques for enantiomers separation were not well developed, and the selective pharmacokinetic study was almost nonexistent. Pharmacokinetics of enantiomers may be stereoselective [8] , [9] , [10] , [11] , [12] , and chiral inversion may occur [13] , [14] , [15] , [16] in vivo or in vitro; hence the pharmacokinetic and chiral inversion studies of enantiomers become necessary. Fig.…”
A high-performance liquid chromatography coupled with mass spectrometry (HPLC–MS) method was established for the separation and determination of acetyl-glutamine enantiomers (acetyl-L-glutamine and acetyl-D-glutamine) simultaneously. Baseline separation was achieved on Chiralpak AD-H column (250 mm × 4.6 mm, 5 µm). n-Hexane (containing 0.1% acetic acid) and ethanol (75:25, v/v) were used as mobile phase at a flow rate of 0.6 mL/min. The detection was operated in the negative ion mode with an ESI source. [M-H]−m/z 187.0540 for enantiomers and [M-H]−m/z 179.0240 for aspirin (IS) were selected as detecting ions. The linear range of the calibration curve for each enantiomer was 0.05–40 µg/mL. The precision of this method at concentrations of 0.5–20 µg/mL was within 7.23%, and the accuracy was 99.81%–107.81%. The precision at LOQ (0.05 µg/mL) was between 16.28% and 17.56%, which was poor than that at QC levels. The average extraction recovery was higher than 85% for both enantiomers at QC levels. The pharmacokinetics of enantiomers was found to be stereoselective. There was not chiral inversion in vivo or in vitro between enantiomers.
“…A-Gln was approved in clinical use about 50 years ago, but the techniques for enantiomers separation were not well developed, and the selective pharmacokinetic study was almost nonexistent. Pharmacokinetics of enantiomers may be stereoselective [8] , [9] , [10] , [11] , [12] , and chiral inversion may occur [13] , [14] , [15] , [16] in vivo or in vitro; hence the pharmacokinetic and chiral inversion studies of enantiomers become necessary. Fig.…”
A high-performance liquid chromatography coupled with mass spectrometry (HPLC–MS) method was established for the separation and determination of acetyl-glutamine enantiomers (acetyl-L-glutamine and acetyl-D-glutamine) simultaneously. Baseline separation was achieved on Chiralpak AD-H column (250 mm × 4.6 mm, 5 µm). n-Hexane (containing 0.1% acetic acid) and ethanol (75:25, v/v) were used as mobile phase at a flow rate of 0.6 mL/min. The detection was operated in the negative ion mode with an ESI source. [M-H]−m/z 187.0540 for enantiomers and [M-H]−m/z 179.0240 for aspirin (IS) were selected as detecting ions. The linear range of the calibration curve for each enantiomer was 0.05–40 µg/mL. The precision of this method at concentrations of 0.5–20 µg/mL was within 7.23%, and the accuracy was 99.81%–107.81%. The precision at LOQ (0.05 µg/mL) was between 16.28% and 17.56%, which was poor than that at QC levels. The average extraction recovery was higher than 85% for both enantiomers at QC levels. The pharmacokinetics of enantiomers was found to be stereoselective. There was not chiral inversion in vivo or in vitro between enantiomers.
“…The intent of this note is to further critically evaluate the published data and provide additional perspectives. Despite the well-planned experimental design that involved time dependent pharmacokinetic sampling from the various tissues, the authors have failed to report the stereoselective pharmacokinetics of ketolorac derived from plasma in this study [1]. Such data would have enabled comparing and contrasting the tissue levels with those observed in the plasma for both ketolorac enantiomers.…”
mentioning
confidence: 98%
“…The investigation of Dubey et al (2013) showed that stereoselectivity of ketolorac was not entirely dependent on the presystemic metabolism although the propensity in the observed stereoselectivity appeared to be different after intravenous as compared to that of the oral administration [2,3]. In view of the earlier reported stereoselective pharmacokinetics of ketolorac and the possibility for chiral inversion in certain tissues, the recent work of Dubey et al (2015) assumes high importance [1]. Hitherto a detailed tissue distribution study of ketolorac enantiomers in the rats examining the pharmacokinetics has not been reported in the literature.…”
mentioning
confidence: 99%
“…have described the enantioselective tissue distribution of ketolorac in the rats [1]. Although the distribution of the enantiomers of ketolorac and racemate was evaluated in 4 important tissues, namely: heart, lungs, liver and kidney, the key generic message that stereoselective plasma pharmacokinetics may not be reflected in all the tissues are effectively conveyed [1]. The intent of this note is to further critically evaluate the published data and provide additional perspectives.…”
mentioning
confidence: 99%
“…Hitherto a detailed tissue distribution study of ketolorac enantiomers in the rats examining the pharmacokinetics has not been reported in the literature. Using the stereoselective plasma pharmacokinetic data from the earlier work for ketolorac enantiomers [2], if one examines the tissue pharmacokinetics of ketolorac enantiomers the following deductions can be arrived at: a) heart, lung and liver tissue pharmacokinetic data showed no stereoselectivity in the pharmacokinetics of ketolorac enantiomers [1] suggesting that the uptake to these tissues presumably by uptake transporters may favour S-ketolorac over the R-enantiomer; b) kidney tissue pharmacokinetic data of both ketolorac enantiomers [1] appeared to be consistent with the plasma pharmacokinetic data with respect to stereoselectivity [2]. Since the elimination of ketolorac is governed by both renal and non-renal mechanisms in the rat [4], the observed stereoselectivity in the plasma may be partly explained by the faster renal excretion of the S-ketolorac as compared to that of the R-enantiomer.…”
The present work aims to develop and validate a simple, rapid, and reproducible reverse phase ultra-fast liquid chromatography method with a UV detector (RP-UFLC-UV) was developed for the separation and determination of sitagliptin (STG) enantiomers (S-(STG) and R-(STG)) simultaneously. Baseline separation was achieved on Lux cellulose-1 column, (cellulose tri-(3,5-dimethyl phenyl carbamate (Chiralcel OD-RH, 250 mm × 4.6 mm, 5 µm) column and mobile phase consisted of 20mM borate buffer solution (pH = 9±0.05) and ACN in the ratio of (60:40, v/v) at a flow rate of 0.8 mL/min was used. Detection of peaks was monitored at 262 nm. For analyzing the STG enantiomers in the rat serum and pure API, a method was developed using the chiral RP-UFLC-UV method was validated. The single oral dose of 2.5 mg/kg of STG racemate was administered to a group of 6 healthy rats for a comparative pharmacokinetic study of both the enantiomers. The linear range of the calibration curve for each enantiomer was 0.5–64 µg/mL. The
precision of this method at concentrations between 0.5–48 µg/mL was within 8.65% and the % recovery
(accuracy) of both sitagliptin (STG) enantiomers (S-(STG) and R-(STG) were 98.47–101.02% and 98.93-
100.52%. The precision at LLOQ (0.5 µg/mL) was between 8.65%-7.09%, which was poor than that at QC
levels, and the average extraction recovery was higher than 85% for both sitagliptin (SGT) enantiomers
at QC levels, and its pharmacokinetics of enantiomers was found to be stereoselective.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
