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A Simple and Sensisitive HPLC Method to Monitor Serum and Synovial Fluid Concentrations of Ketorolac in Reumathologic Patients
Abstract
A rapid, selective and sensitive isocratic reversed-phase HPLC assay coupled with UV detection for quantification of ketorolac in serum and synovial fluid samples has been developed. Analytes were extracted on solid-phase cartridges (SPE) and chromatographic separation was achieved on a C18 column.The chromatographic peak area ratio based on UV absorbency at 313 nm was used for quantitative analysis. This HPLC method has been successfully used for routine evaluation to monitor serum and synovial fluid concentrations in reumathologic patients affering to our institute. Thanks to its sensitivity, this HPLC/UV method is also suitable for pharmacokinetic studies.
... Ketorolac tromethamine works by blocking the production of prostaglandins, compounds that cause pain, fever and inflammation [3]. Ketorolac tromethamine (C 19 H 24 N 2 O 6 ) has a molecular weight 376.4 g/mol and it was estimated by various analytical methods such as spectrophotometry [4][5][6], HPTLC [7,8], voltammetry [9], fluorophotometry [10], HPLC [11][12][13] and in biological fluids such as human plasma [14], human serum [15], human eye samples [16], serum and synovial fluids [17] and post mortem blood samples [18] in the literature. In the present study the authors have proposed five UV spectrophotometric methods for the determination of Ketorolac tromethamine in pharmaceutical dosage forms and the methods were validated as per ICH guidelines [19]. ...
... Literature survey reveals that Ketorolac tromethamine was estimated by various analytical methods such as HPLC [4-6], HPTLC [7,8], fluorophotometry [9], voltammetry [10], spectrophotometry [11][12][13] and in biological fluids such as human serum [14], human plasma [15], human eye samples [16], post mortem blood samples [17] and serum and synovial fluids [18]. In the present study the authors have proposed five UV spectrophotometric methods for the determination of Ketorolac tromethamine in pharmaceutical dosage forms and the methods were validated as per ICH guidelines [19]. ...
... In the past few years, advancements in detection techniques and modification in stationary phases resulted in improved sensitivity and reproducibility of chromatography methods. HPLC is a robust, reliable and reproducible analytical technique that allows the separation of individual compounds from a complex mixture and widely used in quantitative analysis of active ingredients [38,39], impurities [40][41][42][43] and drugs/dosage forms [44,45], monitoring the concentration of drug in blood of patients [46][47][48][49] as well as bioequivalence assessment [50,51]. However, a lot of research has been done to improve the sensitivity of the HPLC method by incorporating new detection techniques and by modifying stationary phases. ...
Bioengineered polymers and nanomaterials have emerged as promising and advanced materials for fabrication and development of novel biosensors. Nanotechnology-enabled biosensor methods have high sensitivity, selectivity and more rapid detection of analyte. Biosensor based methods are more rapid and simple with higher sensitivity and selectivity and can be developed for point-of-care diagnostic testing.Development of a simple, sensitive and rapid method for sorbitol detection is of great significance to efficient monitoring of diabetes-associated disorders like cataract, neuropathy and nephropathy at initial stages. This issue encourages us to write a review which highlight recent advancement in the field of sorbitol detection as no such reports have been published till the date. The first section of this review will be dedicated to the conventional approaches or methods that had been played a role in detection. The second part will focus on the emerging field i.e. biosensors with optical, electrochemical, piezoelectric etc. approachesfor sorbitol detection and importance of its detection in healthcare application. It is expected that this review will be very helpful for readers to know the different conventional and recent detection techniques for sorbitol at a glance.
... [7][8][9][10] A few analytical and bioanalytical methods have been reported in the literature for the determination of KETO alone or in combination with other drugs. It includes determination of KETO in biological samples by using LC and LC/MS methods [11][12][13][14][15][16][17][18][19][20][21] as well as LC/MS/MS method, [22] in vivo metabolites identification, [23] spectrophotometric estimation of KETO by different methods, [24] determination of KETO by HPTLC, [25] determination of KETO and its impurities by capillary electrochromatography, [26] assay of KETO in pharmaceutical matrices using differential pulse polarography, [27] derivative adsorptive chronopotentiometry, [28] and high-performance liquid chromatography (HPLC) methods. [29][30][31] The hydrolytic degradation behavior of KETO was studied under acidic and alkaline conditions by Salaris et al. [32] One acid hydrolysis product was identified that is listed in British Pharmacopoeia as impurity H, chemically known as methyl (1RS)-5-benzoyl-2,3dihydro-1H-pyrrolizine-1-carboxylate (Scheme 1, structure K-8). ...
Ketorolac, a nonsteroidal anti-inflammatory drug, was subjected to forced degradation studies as per International Conference on Harmonization guidelines. A simple, rapid, precise, and accurate high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (LC/ESI/Q/TOF/MS/MS) method has been developed for the identification and structural characterization of stressed degradation products of ketorolac. The drug was found to degrade in hydrolytic (acidic, basic, and neutral), photolytic (acidic, basic, and neutral solution), and thermal conditions, whereas the solid form of the drug was found to be stable under photolytic conditions. The method has shown adequate separation of ketorolac tromethamine and its degradation products on a Grace Smart C-18 (250 mm × 4.6 mm i.d., 5 µm) column using 20 mM ammonium formate (pH = 3.2): acetonitrile as a mobile phase in gradient elution mode at a flow rate of 1.0 ml/min. A total of nine degradation products were identified and characterized by LC/ESI/MS/MS. The most probable mechanisms for the formation of degradation products have been proposed on the basis of a comparison of the fragmentation of the [M + H]+ ions of ketorolac and its degradation products. In silico toxicity of the drug and degradation products was investigated by using topkat and derek softwares. The method was validated in terms of specificity, linearity, accuracy, precision, and robustness as per International Conference on Harmonization guidelines. Copyright © 2014 John Wiley & Sons, Ltd.
... A detailed literature survey revealed that a number of methods are available for determination of KTR, SMP and SPP individual in serum by high-performance liquid chromatography (HPLC) [8][9][10][11][12][13][14][15][16][17] , gas chromatography mass spectrometry [18] , spectrophotometry [19,20] , liquid chromatography mass spectrometry [21] , and in pharmaceutical dosage form by HPLC [22][23][24][25] . ...
A sensitive, fast, and stability-indicating isocratic reverse-phase ultra-performance liquid chromatography method was developed and validated for quantitative simultaneous determination of sodium methylparaben, sodium propylparaben and ketorolac tromethamine in topical dosage forms. Separation of all peaks was achieved by using acquity ethylene bridged hybrid C18 (50×2.1 mm, 1.7 μ) as stationary phase, mobile phase used was triethylamine buffer (pH 2.5):tetrahydrofuran:methanol (665:35:300, v/v/v) with isocratic mode at a flow rate of 0.40 ml/min. All component were detected at 252 nm with 10 min run time. The described method was found to be linear in the concentration range of 248-744 μg/ml for ketorolac tromethamine, 20.8-62.4 μg/ml for sodium methylparaben and 2.38-7.13 μg/ml for sodium propylparaben with correlation coefficients more than 0.999. Method was validated in terms of specificity, linearity, accuracy, precision, solution stability, filter equivalency, and robustness as per International Conference on Harmonization guideline. Formulation was exposed to the stress conditions of peroxide, acid, base, thermal, and photolytic degradation and proven all components were well separated in the presence of degradants.
... The majority of the methods available for its quantification are chromatographic ones, such as thin-layer chromatography with densitometry detection, [4] micellar electrokinetic chromatography with UV detection, [5] liquid chromatography with UV, [6][7][8][9] and mass spectrometry [10] as detection techniques. Gas chromatography coupled to mass spectrometry has also been described [11,12] for the analysis of blood samples. ...
An automatic fluorescence method was developed for the determination of ketorolac tromethamine. The method is based on the direct oxidation of the analyte by an acidic solution of permanganate, being the resulting fluorescence measured at 227 nm/320 nm (λex/λem). The reaction is carried out online due to the use of the Sequential Injection Analysis methodology. A detection limit of 0.12 µ g mL and a R.S.D. lower than 3% (n = 10) were obtained under optimum conditions. The analyte was satisfactorily determined in pharmaceuticals and urine samples. Recovery experiments were carried out on human urine, with recoveries in the range 92–108%.
... It is indicated for the short-term management of moderate to severe pain. Literature survey showed that very few analytical methods have been reported for the estimation of ketorolac in single or in combination such as spectrophotometric [5] , flow injection analysis [6] , high-performance liquid chromatography (HPLC) [7][8][9][10][11][12][13][14][15] , high-performance thin layer chromatography (HPTLC) [16] and gas chromatography-mass spectrometry [17] , which are either less economical or less sensitive. For routine analysis, a simple, rapid and most sensitive analytical method is preferred. ...
A reliable, rapid and sensitive isocratic reverse phase high-performance liquid chromatography method has been developed and validated for assay of ketorolac tromethamine in tablets and ophthalmic dosage forms using diclofenac sodium as an internal standard. An isocratic separation of ketorolac tromethamine was achieved on Oyster BDS (150×4.6 mm i.d., 5 μm particle size) column using mobile phase of methanol:acetonitrile:sodium dihydrogen phosphate (20 mM; pH 5.5) (50:10:40, %v/v) at a flow rate of 1.0 ml/min. The eluents were monitored at 322 nm for ketorolac and at 282 nm for diclofenac sodium with a photodiode array detector. The retention times of ketorolac and diclofenac sodium were found to be 1.9 min and 4.6 min, respectively. Response was a linear function of drug concentration in the range of 0.01-15 μg/ml (R (2)=0.994; linear regression model using weighing factor 1/x (2)) with a limit of detection and quantification of 0.002 μg/ml and 0.007 μg/ml, respectively. The % recovery and % relative standard deviation values indicated the method was accurate and precise.
ABSTRACT
A simple, fast, precise, selective and accurate RP-HPLC method was developed and validated for the simultaneous determination of Febuxostat and Ketorolac from bulk and formulations. Chromatographic separation was achieved isocratically on a Waters C18 column (250×4.6 mm, 5 μ particle size) using a mobile phase, Methanol and Ammonium acetate buffer (adjusted to pH 6.0 with 1% orthophosphoric acid) in the ratio of 60:40. The flow rate was 1 ml/min and effluent was detected at 321nm. The retention time of Febuxostat and Ketorolac were 2.62 min and 3.96 min. respectively. Linearity was observed in the concentration range of 5-30μg/ml and 10-60 μg/ml for Febuxostat and Ketorolac respectively with correlation coefficient 0.999 for both the drugs. Percent recoveries obtained for both the drugs were 99.94-99.22% and 99.44-101.06%, respectively. The method was validated according to the ICH guidelines with respect to specificity, linearity, accuracy, precision and robustness. The method developed can be used for the routine analysis of Febuxostat and Ketorolac from their combined dosage form.
Key words: RP-HPLC Method; UV-VIS detection; Febuxostat and Keterolac; Tablet dosage forms.
In this work, porphyrin-functionalized graphene oxide nanosheets (GO@meso-tetrakis(4-hydroxyphenyl)porphyrin) were synthesized and employed as the sorbent. Porphyrins owing to their unique structures and tunable terminal functional groups are expected to be promising media for extraction of the desired analytes. Also, GO with a high specific surface area has exhibited good potential for the extraction purposes. Inspired by these intriguing properties, the combination of GO and porphyrin can benefit both of these amazing features. The synthesized sorbent was utilized for micro solid phase extraction of non-steroidal anti-inflammatory drugs followed by HPLC-UV. Optimization of the experimental factors including sorbent amount, sample pH, sample and eluent flowrates, eluent volume, and the number of desorption cycles were performed with the aid of central composite design. Under the optimal conditions, the calibration curves were linear within the range of 2.0-600 ng mL-1 and limits of detection were found between 0.5-2.0 ng mL-1. The preconcentration factors and absolute recoveries were obtained in the range of 4.80-9.79 and 29%-59%, respectively. The matrix effect for the urine samples varied between 81.9%-91.6% at two concentrations of 50 and 300 ng mL-1, respectively. Intra- and inter-day RSD% (n = 3) of the spiked urine samples at three level concentrations of 25, 100, and 300 ng mL-1 were less than 10%. The relative recoveries of the urine samples were calculated in the range of 85.2-98.6%. Eventually, the method exhibits proper sensitivity, excellent repeatability, high reusability, and acceptable precision and accuracy.
A simple, fast, precise, selective and accurate RP-HPLC method was developed and validated for the simultaneous determination of Febuxostat and Ketorolac from bulk and formulations. Chromatographic separation was achieved isocratically on a Waters C18 column (250×4.6 mm, 5 µ particle size) using a mobile phase, Methanol and Ammonium acetate buffer (adjusted to pH 6.0 with 1% orthophosphoric acid) in the ratio of 60:40. The flow rate was 1 ml/min and effluent was detected at 321nm. The retention time of Febuxostat and Ketorolac were 2.62 min and 3.96 min. respectively. Linearity was observed in the concentration range of 5-30µg/ml and 10-60 µg/ml for Febuxostat and Ketorolac respectively with correlation coefficient 0.999 for both the drugs. Percent recoveries obtained for both the drugs were 99.75-100.06% and 98.63-99.93%, respectively. The method was validated according to the ICH guidelines with respect to specificity, linearity, accuracy, precision and robustness. The method developed can be used for the routine analysis of Febuxostat and Ketorolac from their combined dosage form
In order to enhance the sensitivity and to develop a faster direct method for plasma and urine quantification of racemic ketorolac, its metabolites (p-hydroxy-ketorolac and ketorolac glucuronides) and ketorolac enantiomers, we developed an extraction procedure based on solid-phase extraction combined with specific and fast chromatographic separation. Extraction and chromatography resulted in cleaner chromatograms without interfering compounds. In both plasma and urine, linearity of the standard curves for racemic ketorolac and p-hydroxy-ketorolac was validated in the concentration range 0.025–10 mg L−1, while for ketorolac enantiomers in the concentration range 0.025–5 mg L−1. The lower limit of quantification was two times lower than in earlier described methods. The developed method was suitable for direct quantification of racemic ketorolac, p-hydroxy-ketorolac and ketorolac enantiomers in plasma and urine samples in women at delivery and in postpartum, enabling us to document significant intra-individual differences in pharmacokinetics between these physiological states.
A fast, sensitive, and accurate stability indicating reverse phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for simultaneous determination of gatifloxacin and ketorolac tromethamine in combined dosage form. Chromatographic separations were achieved on BDS Hypersil C8 column (250 × 4.6 mm) with mobile phase that consisted of methanol and phosphate buffer (pH 3.0) in the ratio of (55:45 v/v) at a flow rate of 1.5 m Lmin. The analytes were detected at 270 nm using ultraviolet detection. The retention times of gatifloxacin and ketorolac tromethamine were found to be 2.460 and 6.366 min, respectively. When forced degradation studies were applied to both the drugs in combination, it was found that both gatifloxacin and ketorolac tromethamine were very stable under the basic, acidic, wet heat and oxidative environment. The method was linear in the concentration range of 30–90 µg mL for gatifloxacin and 50–110 µg mL for ketorolac tromethamine. The correlation coefficients were found to be 0.9998 and 0.9999 for gatifloxacin and ketorolac tromethamine, respectively. The method resulted in good separation of both the analytes with acceptable tailing and resolution. The developed method can be used for routine determination of gatifloxacin and ketorolac tromethamine in commercial formulations.
A simple, RP-HPLC method was established for determining moxifloxacin and ketorolac in pharmaceutical formulations. Moxifloxacin, ketorolac and their degradation products were separated using C8 column with methanol and phosphate buffer pH 3.0 (55:45 v/v) as the mobile phase. Detection was performed at 243 nm using a diode array detector. The method was validated using ICH guidelines and was linear in the range 20-140 µg mL-1 for both analytes. Good separation of both the analytes and their degradation products was achieved using this method. The developed method can be applied successfully for the determination of moxifloxacin and ketorolac.
A simple, specific and accurate stability indicating liquid chromatographic method is established for simultaneous determination of ofloxacin and ketorolac tromethamine in bulk drugs and pharmaceutical formulations. Optimum chromatographic separations among ofloxacin, ketorolac and stress-induced degradation products have been achieved within 15 min by using a BDS Hypersil C8 column (250 × 4.6 mm, 5 μm) as the stationary phase with methanol and phosphate buffer pH 3.0 (55:45 v/v) as the mobile phase at a flow rate of 0.8 mL min−1. Detection is performed at 270 nm using a diode array detector. The method is validated in accordance with ICH guidelines. The response is a linear function of concentration over the range of 12–84 μg mL−1 for ofloxacin and 20–140 μg mL−1 for ketorolac tromethamine. The method results in excellent separation of analytes and their stress induced degradation products with acceptable tailing and resolution. The peak purity index for both the analytes after all types of stress is >0.999 indicating complete separation of both analyte peaks from the stress induced degradation products. The method can therefore be regarded as stability-indicating. The developed method can be applied successfully for simultaneous determination of ofloxacin and ketorolac in pharmaceutical formulations and their stability studies.
Ketorolac tromethamine, a nonnarcotic, prostaglandin synthesis-inhibiting analgesic, was compared with morphine sulfate for relief of moderate to severe postoperative pain. The 155 patient participants received single intramuscular doses of either ketorolac, 10, 30, or 90 mg, or morphine, 6 or 12 mg, administered in a double-blind, randomized fashion. Pain scores (verbal and visual analog) were recorded at baseline and assessed at 30 minutes and then hourly to 6 hours. Pain relief was rated at the same times. Ketorolac, 90 and 30 mg, was rated significantly better than morphine, 6 mg, at each assessment interval after 1 hour. Ketorolac, 90 and 30 mg, was rated similarly to morphine, 12 mg, for the first 3 hours and better than morphine, 12 mg, 4 hours after injection. There were no serious side effects reported. The only side effect reported in more than 3% of patients was 8% somnolence with morphine. This study shows ketorolac to be a safe and effective analgesic for relief of postoperative pain.
The purpose of this study was to investigate the stereospecific pharmacokinetics of ketorolac (KT) in goats following a single 2 mg/kg intravenous (i.v.) dose and a single 6 mg/kg oral dose. A stereoselective high pressure liquid chromatography assay was used to quantify ketorolac plasma concentrations. Pharmacokinetic parameters for both stereoisomers were estimated by model independent methods. Following an i.v. dose, the plasma concentration profiles for the stereoisomers were similar with half-lives of 1.05 +/- 0.62 h for R-KT and 1.05 +/- 0.61 h for S-KT. Clearance values for R- and S-KT after an i.v. dose were 0.53 +/- 0.23 and 0.54 +/- 0.23 L.h/kg, respectively. Following an oral dose, the terminal half-lives were longer with values of 34.08 +/- 11.81 and 33.97 +/- 12.19 h for R-KT and S-KT, respectively. The average bioavailability was 133 +/- 23% for R-KT and S-KT, respectively. The longer half-lives and high apparent bioavailability after oral dosing are suggestive of a slow absorption process in the gastrointestinal tract and recycling. The results indicate that interconversion of the stereoisomers of ketorolac is absent in goats. However, studies with individual isomers are needed before any conclusion can be drawn about the lack of bioinversion.
Ketorolac tromethamine (ie, ketorolac) is an NSAID that appears to have several mechanisms of action, including inhibition of prostaglandin synthesis, modulatory effect on opioid receptors, and nitric oxide synthesis. Ketorolac is used in the treatment of pain. There are various generic formulations of sublingual ketorolac available in Mexico. However, a literature search did not identify published data concerning the bioavailability of these formulations in the Mexican population.
The aim of this study was to compare the bioavailability of 2 sublingual formulations of ketorolac 30-mg tablets in healthy Mexican adult volunteers.
This was a randomized-sequence, open-label, single-dose, 2-period crossover (2 dosing periods x 2 treatments) study comparing the bioavailability of two 30-mg sublingual tablet formulations of ketorolac. Healthy Mexican adult (aged, 18-55 years) men and women were eligible for inclusion. Subjects were randomly assigned in a 1:1 ratio to receive a single dose of the test formulation or the reference formulation. After a 12-hour overnight fast, subjects received a single dose of the corresponding formulation. There was a 7-day washout period between administration periods. Plasma samples were obtained over a 24-hour period after administration. Plasma ketorolac concentrations were analyzed by high-performance liquid chromatography for analysis of pharmacokinetic properties, including Cmax, AUC0-24, and AUC0-infinity. Blood samples were drawn immediately after sublingual placement of the drug and at 10, 20, 30, 40, 50, 60, 75, and 90 minutes and 2, 4, 6, 8, 10, 12, and 24 hours after dosing. The formulations were considered bioequivalent if the geometric mean ratios of Cmax and AUC were within the predetermined range of 80% to 125% and if P for the 90% CIs was <0.05. Tolerability was assessed by vital sign monitoring, laboratory analysis results, and subject interviews.
A total of 27 subjects (18 women, 9 men; mean [SD] age, 27 [9] years [range, 18-47 years]; weight, 61 [8] kg [48-79 kg]; height, 163 [8] cm [150-180 cm]) were enrolled and completed the study. Fourteen subjects received the test formulation first. No period or sequence effect was observed. The 90% CIs for the corresponding differences in natural log Cmax, AUC0-24, and AUC0-infinity were 95.94% to 114.66%, 98.34% to 105.90%, and 99.25% to 108.36%, respectively (all, (P) < 0.05), meeting the predetermined criteria for bioequivalence. Sixteen subjects experienced a total of 20 adverse events (AEs) during the study. None of the AEs were considered serious. One AE (nausea) appeared to be related to use of the reference formulation. Conclusions: In this small study in 27 healthy Mexican adult volunteers, the test formulation of a single, 30-mg sublingual tablet of ketorolac appeared to be bioequivalent to the reference formulation based on the rate and extent of absorption. Both formulations were well tolerated.
The efficacy of a single dose of intramuscular ketorolac 10 mg or 90 mg was compared with pethidine 100 mg in a randomized double-blind study in 121 patients reporting at least moderate pain due to renal colic. Pain was assessed before drug administration, and then at 1 hour and 12 hours after the dose. Sedation was also assessed at these times, and additionally at the 12 hour assessment the time of the next analgesic dose was recorded. At 1 hour after dosing, pain scores had decreased in all groups; the largest decrease was seen in the ketorolac 90 mg group. The difference in the decrease was significant between the two ketorolac groups, but the differences between ketorolac and pethidine were not significant. Fewer patients in the ketorolac 90 mg group (17%) required a further dose of analgesic within 10 hours than in either the ketorolac 10 mg group (39%) or the pethidine 100 mg group (47%). The difference between ketorolac 90 mg and pethidine 100 mg was statistically significant. At both assessment times the proportion of patients with no sedation was higher in the two ketorolac groups than in the pethidine group. The overall incidence of adverse events was low with all drugs, notably so for the occurrence of vomiting after ketorolac. The results of the study show that intramuscular ketorolac is efficacious in the treatment of renal colic.
To evaluate the efficacy of IM ketorolac versus that of oral ibuprofen in acute musculoskeletal pain.
Randomized, prospective, double-blind clinical trial.
Urban teaching emergency department with an annual census of 43,000.
Convenience sample of 82 patients aged 18 to 70 years with acute musculoskeletal pain due to trauma.
Forty-two subjects each received 60 mg ketorolac by IM injection and ingested a placebo capsule. Forty subjects each ingested 800 mg ibuprofen and received a placebo (saline) IM injection. Pain was evaluated with a 100-mm visual analog scale at baseline and 15, 30, 45, 60, 75, 90, and 120 minutes after dosing. The prevalence of side effects was elicited in each patient.
Mean pain scores improved in each group during the course of the study but did not significantly differ between groups at baseline or at any subsequent interval. The numbers of dropouts due to inadequate analgesia and prevalence of side effects in the two groups did not differ significantly.
IM ketorolac and oral ibuprofen provide comparable analgesia in ED patients with acute musculoskeletal pain.
An improved high-performance liquid chromatographic method has been developed to measure human plasma concentrations of the analgesic nonsteroidal anti-inflammatory drug ketorolac for use in pharmacokinetic studies. Samples were prepared for analysis by solid-phase extraction using Bond-Elut PH columns, with nearly complete recovery of both ketorolac and the internal standard tolmetin. The two compounds were separated on a Radial-Pak C18 column using a mobile phase consisting of water-acetonitrile-1.0 mol/l dibutylamine phosphate (pH 2.5) (30:20:1) and detected at a UV wavelength of 313 nm. Using only 250 microl of plasma, the standard curve was linear from 0.05 to 10.0 microg/ml.
The purpose of this study was to establish the stereospecific pharmacokinetics of ketorolac (KT) in calves following a single 2 mg/kg intravenous (i.v.) and a single 8 mg/kg oral dose. Plasma concentrations were determined using a stereoselective HPLC assay. Pharmacokinetic parameters for both the stereoisomers were estimated by model-independent methods. Following an i.v. dose, the plasma concentration profiles of the stereoisomers were similar with half-lives of 5.9 +/- 5.1 h for R-KT and 6.0 +/- 4.9 h for S-KT. Clearance values for R- and S-KT after an i.v. dose were 0.0470 +/- 0.0370 and 0.0480 +/- 0.0370 L/h/kg respectively. After an oral dose, the terminal half-lives were longer than following i.v. administration with values of 14.77 +/- 3.08 and 14.55 +/- 2.95 h for R-KT and S-KT respectively. The average oral bioavailability was 86.5 +/- 20.6% for R-KT and 86.7 +/- 20.3% for S-KT. The results indicate that the stereoisomers of KT have similar pharmacokinetic profiles in calves. Although, unlike humans, bioinversion between KT stereoisomers appears minimal in calves, studies with individual isomers are needed before any firm conclusions can be drawn about this lack of KT bioinversion.