Determination of Racemic Ketorolac, Ketorolac Enantiomers and Their Metabolites in Human Plasma and Urine by LC–UV, Applied in Clinical Study During and After Pregnancy

Kulo, Aida; Mulabegović, Nedžad; Loga-Zec, Svjetlana; Allegaert, Karel; Hoon, Jan de; Verbesselt, René

doi:10.1007/s10337-014-2670-4

Cited by 3 publications

(8 citation statements)

References 36 publications

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“…After centrifugation, plasma was separated and frozen at −20°C until subsequent analysis. The samples were measured by high‐performance liquid chromatography (HPLC) after solid‐phase column extraction (Oasis HLB 30 mg, 1 ml volume, Waters, Milford, MA, USA) . R‐ and S‐enantiomers were separated on a chiral AGP column (5 μ, 100 × 40 mm).…”

Section: Methodsmentioning

confidence: 99%

“…Quantification was attained using ultraviolet (UV) detection at 313 nm. The lower limit of quantification (LLOQ) of the used method was 0.025 mg l –1 for both enantiomers and the limit of detection (LOD) was 0.01 mg l –1 .…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies in other patient groups have also shown significant differences in pharmacokinetics between R‐ and S‐enantiomers . Recently, a stereo‐specific quantification method in plasma has been reported, allowing the precise measurement of the two enantiomers , which made the idea of a stereo‐selective pharmacokinetic study at the time of delivery and in postpartum feasible.…”

Section: Introductionmentioning

confidence: 99%

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Body weight, gender and pregnancy affect enantiomer‐specific ketorolac pharmacokinetics

Välitalo

Kemppainen

Kulo

et al. 2017

Brit J Clinical Pharma

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Body weight, gender and pregnancy affect enantiomer‐specific ketorolac pharmacokinetics

Välitalo

Kemppainen

Kulo

et al. 2017

Brit J Clinical Pharma

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“…SPE columns were used before injecting the reconstituted extract sample (volume varied between 10 and 60 mL) onto the chiral column. Direct resolution and quantification of enantiomers of Ket was achieved in such samples of plasma and urine using chiral AGP column and a mixture of isopropyl alcohol and 50 mM potassium dihydrogen phosphate buffer pH 5.5 (5:95, v/v for plasma and 4:96, v/v for urine) as the mobile phase at a flow rate of 1.0 and 0.5 mL min À1 , respectively with UV detection at 313 nm [30]. The LLOQ for [(R)-(þ)-] and [(S)-(À)-Ket] was 0.025 mg L À1 .…”

Section: Lynn Et Al In 2007 Reportedmentioning

confidence: 99%

Liquid chromatographic enantioseparation, determination, bioassay and isolation of enantiomers of Ketorolac: A review

Bhushan

2022

AChrom

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Ketorolac (Ket) is a potent non-narcotic analgesic drug (among the nonsteroidal anti-inflammatory drugs). The physiological activity of Ket resides with (S)-(−)-Ket while the drug is marketed and administered as a racemic mixture. Therefore, it is desirable that the pharmacokinetics is measured and quantified for enantiomers individually and not as a total drug. The present paper is focused on relevant literature on LC enantioseparation of (RS)-Ket along with bioassay, pharmacokinetic and clinical studies within the discipline of analytical chemistry. HPLC and Thin layer chromatography (TLC) methods using both direct and indirect approaches are discussed. The methods provide chirality recognition even in the absence of pure enantiomers. Besides, a brief discussion on resolution by crystallization and enzymatic methods is included. The most interesting aspects include establishment of structure and molecular asymmetry of diastereomeric derivatives using LC-MS, proton nuclear magnetic resonance spectrometry, and by drawing conformations in three dimensional views by using certain software. A brief discussion has also been provided on the recovery of native enantiomers by TLC.

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“…Blood samples were collected in lithium heparinized tubes, centrifuged, and plasma was stored at −20°C until analysis. Plasma concentrations of S-and R-ketorolac were determined using a validated high performance liquid chromatography analysis with UV detection after extraction procedure based on solid-phase extraction [25].…”

Section: Patients Ketorolac Dosing Sample Collection and Sample Hamentioning

confidence: 99%

Enantiomer-specific ketorolac pharmacokinetics in young women, including pregnancy and postpartum period

Kulo

Smits

Maleškić

et al. 2017

Bosn J of Basic Med Sci

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Racemic ketorolac clearance (CL) is significantly higher at delivery, but S-ketorolac disposition determines the analgesic effects. The aim of this study was to investigate the effect of pregnancy and postpartum period on enantiomer-specific (S and R) intravenous (IV) ketorolac pharmacokinetics (PKs). Data in women shortly following cesarean delivery (n=39) were pooled with data in a subgroup of these women that was reevaluated in the later postpartum period (postpartum group, n=8/39) and with eight healthy female volunteers. All women received single IV bolus of 30 mg ketorolac tromethamine. Five plasma samples were collected at 1, 2, 4, 6, and 8 hours and plasma concentrations were determined using high performance liquid chromatography. Enantiomer-specific PKs were calculated using PKSolver. Unpaired analysis showed that distribution volume at steady state (Vss, L/kg) for S- and R-ketorolac was significantly higher in women shortly following cesarean delivery (n=31) compared to postpartum group (n=8) or to healthy female volunteers (n=8). CL, CL to body weight, and CL to body surface area (CL/BSA) for S- and R-ketorolac were also significantly higher in women following delivery. In addition, S/R-ketorolac CL/BSA ratio was significantly higher at delivery. Paired PK analysis in eight women shortly following delivery and in postpartum group showed the same pattern. Finally, the simultaneous increase in CL and Vss resulted in similar estimates for elimination half-life in both unpaired and paired analysis. In conclusion, pregnancy affects S-, R-, and S/R-ketorolac disposition. This is of clinical relevance since S-ketorolac (analgesia) CL is even more increased compared to R-ketorolac CL, and S/R-ketorolac CL ratio is higher following delivery compared to postpartum period or to healthy female volunteers.

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Determination of Racemic Ketorolac, Ketorolac Enantiomers and Their Metabolites in Human Plasma and Urine by LC–UV, Applied in Clinical Study During and After Pregnancy

Cited by 3 publications

References 36 publications

Body weight, gender and pregnancy affect enantiomer‐specific ketorolac pharmacokinetics

Body weight, gender and pregnancy affect enantiomer‐specific ketorolac pharmacokinetics

Liquid chromatographic enantioseparation, determination, bioassay and isolation of enantiomers of Ketorolac: A review

Enantiomer-specific ketorolac pharmacokinetics in young women, including pregnancy and postpartum period

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