Simultaneous measurement of the major metabolites of dolasetron mesilate in human urine using solid-phase extraction and high-performance liquid chromatography

Sanwald, Patricia; Huebert, Norman; Haegele, K.D.

doi:10.1016/s0378-4347(94)80054-5

Cited by 8 publications

(2 citation statements)

References 6 publications

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“… Methods Samples Linear range LOQ Ref. 1 GC–MS Human plasma l–120 ng/mL 1 ng/mL [5] LC Human plasma 5–200 ng/mL – 2 Reversed-phase HPLC Human plasma 5–1000 pmol/mL 10 pmol/mL [6] Urine 20–1000 pmol/mL 50 pmol/mL 3 HPLC Urine 200–5000 pmol/mL [7] 4 HPLC-ESI-MS Human plasma 7.9–4750 ng/mL 7.9 ng/mL [8] 5 Proposed method Human serum and urine 2–40 µg/mL 1.51 µg/mL This work …”

Section: Resultsmentioning

confidence: 99%

“…So far, very few methods have been developed for the analysis of DM in human plasma and urine. Previous methods based on gas chromatography-mass spectrometry (GC–MS) [5] and high performance liquid chromatography (HPLC) [6] , [7] , [8] suffered from poor sensitivity and endogenous interferences or complicated derivatization procedures. In addition, these methods have some limitations like use of expensive instruments, long operation time and reagents required not easily available in many laboratories.…”

Section: Introductionmentioning

confidence: 99%

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CdS nanocrystals as fluorescent probe for detection of dolasetron mesylate in aqueous solution: Application to biomedical analysis

Pawar

Walekar

Kondekar

et al. 2016

Journal of Pharmaceutical Analysis

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A simple and straightforward method for the determination of dolasetron mesylate (DM) in aqueous solution was developed based on the fluorescence quenching of 3-Mercaptopropionic acid (MPA) capped CdS quantum dots (QDs). The structure, morphology, and optical properties of synthesized QDs were characterized by using UV-Vis absorption spectroscopy, fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements. Under the optimum conditions, the MPA-CdS QDs fluorescence probe offered good sensitivity and selectivity for detecting DM. The probe provided a highly specific selectivity and a linear detection of DM in the range of 2–40 µg/mL with detection limit (LOD) 1.512 µg/mL. The common excipients did not interfere in the proposed method. The fluorescence quenching mechanism of CdS QDs is also discussed. The developed sensor was applied to the quantification of DM in urine and human serum sample with satisfactory results.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CdS nanocrystals as fluorescent probe for detection of dolasetron mesylate in aqueous solution: Application to biomedical analysis

Pawar

Walekar

Kondekar

et al. 2016

Journal of Pharmaceutical Analysis

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Stereoselectivity of the carbonyl reduction of dolasetron in rats, dogs, and humans

Dow¹,

Berg²

1995

Chirality

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The initial step in the metabolism of dolasetron or MDL 73,147EF [(2 alpha, 6 alpha, 8 alpha, 9a beta)-octahydro-3-oxo-2,6-methano-2H- quinolizin-8-yl 1H-indol-3-carboxylate, monomethanesulfonate] is the reduction of the prochiral carbonyl group to give a chiral secondary alcohol "reduced dolasetron." An HPLC method, using a chiral column to separate reduced dolasetron enantiomers, has been developed and used to measure enantiomers in urine of rats, dogs, and humans after dolasetron administration. In all cases, the reduction was enantioselective for the (+)-(R)-enantiomer, although the dog showed lower stereoselectivity, especially after iv administration. An approximate enantiomeric ratio (+/-) of 90:10 was found in rat and human urine. The contribution of further metabolism to this enantiomeric ratio was considered small as preliminary studies showed that oxidation of the enantiomeric alcohols by human liver microsomes demonstrated only minor stereoselectivity. Further evidence for the role of stereoselective reduction in man was obtained from in vitro studies, where dolasetron was incubated with human whole blood. The enantiomeric composition of reduced dolasetron formed in human whole blood was the same as that found in human urine after administration of dolasetron. Enantioselectivity was not due to differences in the absorption, distribution, metabolism, or excretion of enantiomers, as iv or oral administration of rac-reduced dolasetron to rats and dogs lead to the recovery, in urine, of essentially the same enantiomeric composition as the dose administered. it is fortuitous that the (+)-(R)-enantiomer is predominantly formed by carbonyl reductase, as it is the more active compound.

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Pharmacokinetics of Dolasetron after Oral and Intravenous Administration of Dolasetron Mesylate in Healthy Volunteers and Patients with Hepatic Dysfunction

Stubbs¹,

Martin²,

Dimmitt³

et al. 1997

The Journal of Clinical Pharma

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In previous studies, dolasetron was shown to have both renal and hepatic elimination mechanisms. This study was conducted to determine the impact of varying degrees of hepatic dysfunction on the pharmacokinetics and safety of dolasetron and its reduced metabolites. Seventeen adults were studied: six healthy volunteers (group I), seven patients with mild hepatic impairment (Child-Pugh class A; group II), and four patients with moderate to severe hepatic impairment (Child-Pugh class B or C1; group III). Single 150-mg doses of dolasetron mesylate were administered intravenously and orally, with a 7-day washout period separating treatments. After intravenous administration, no differences were observed between healthy volunteers and patients with hepatic impairment in maximum plasma concentration (Cmax), areas under the plasma concentration-time curve (AUC), or elimination half-life (t1/2) of intact dolasetron. No significant differences were found in Cmax, AUC, or apparent clearance (C(lapp)) of hydrodolasetron, the primary metabolite of dolasetron. The mean t1/2 increased from 6.87 hours in group I to 11.69 hours in group III. After oral administration, C(lapp) of hydrodolasetron decreased by 42%, and Cmax increased by 18% in patients with moderate to severe hepatic impairment. There were less changes in patients with mildly hepatic impairment. Total percentage of dose excreted as metabolites was similar for healthy volunteers and patients with hepatic impairment, although urinary metabolite profiles differed slightly. Dolasetron was well tolerated and there were no apparent differences in adverse effects between groups or treatments. Because hepatic impairment did not influence Cl(app) of hydrodolasetron after intravenous administration, and the range of plasma concentrations of hydrodolasetron after oral administration was not different from those observed in healthy volunteers, dosage adjustments are not recommended for patients with hepatic disease and normal renal function.

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Simultaneous measurement of the major metabolites of dolasetron mesilate in human urine using solid-phase extraction and high-performance liquid chromatography

Cited by 8 publications

References 6 publications

CdS nanocrystals as fluorescent probe for detection of dolasetron mesylate in aqueous solution: Application to biomedical analysis

CdS nanocrystals as fluorescent probe for detection of dolasetron mesylate in aqueous solution: Application to biomedical analysis

Stereoselectivity of the carbonyl reduction of dolasetron in rats, dogs, and humans

Pharmacokinetics of Dolasetron after Oral and Intravenous Administration of Dolasetron Mesylate in Healthy Volunteers and Patients with Hepatic Dysfunction

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