Determination of lumefantrine in rat plasma by liquid–liquid extraction using LC–MS/MS with electrospray ionization: Assay development, validation and application to a pharmacokinetic study

Wahajuddin,; Singh, Sheelendra Pratap; Jain, Girish Kumar

doi:10.1016/j.jchromb.2009.02.058

Cited by 39 publications

(35 citation statements)

References 12 publications

(19 reference statements)

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“…The extraction recovery of analytes, through liquid-liquid extraction procedure, was determined by comparing the peak areas of extracted plasma (pre-spiked) standard QC samples (n = 6) to those of the post-spiked standards at equivalent concentrations [18,19]. Recoveries of tamoxifen and 4-hydroxytamoxifen were determined at three concentration levels QC low, QC medium and QC high concentrations viz., 2.5, 80, and 160 ng/mL, whereas the recovery of the IS was determined at a single concentration of 5 ng/mL.…”

Section: Recoverymentioning

confidence: 99%

“…The effect of rat plasma constituents over the ionization of tamoxifen, 4-hydroxytamoxifen and IS was determined by comparing the responses of the post-extracted plasma standard QC samples (n = 6) with the response of analytes from neat standard samples at equivalent concentrations [18,19]. The matrix effect for tamoxifen and 4-hydroxytamoxifen was determined at three concentration levels viz., 2.5, 80 and 160 ng/mL whereas the matrix effect over the IS was determined at a single concentration of 5 ng/mL.…”

Section: Matrix Effectmentioning

confidence: 99%

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Liquid chromatography–mass spectrometry method for the quantification of tamoxifen and its metabolite 4-hydroxytamoxifen in rat plasma: Application to interaction study with biochanin A (an isoflavone)

Singh

Wahajuddin

Ali

et al. 2011

Journal of Chromatography B

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Section: Recoverymentioning

confidence: 99%

Section: Matrix Effectmentioning

confidence: 99%

Liquid chromatography–mass spectrometry method for the quantification of tamoxifen and its metabolite 4-hydroxytamoxifen in rat plasma: Application to interaction study with biochanin A (an isoflavone)

Singh

Wahajuddin

Ali

et al. 2011

Journal of Chromatography B

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“…When matrix compounds and analytes enter the ion source at the same time, the ionization efficiency of the analyte might be influenced [21]. The matrix effect was evaluated by comparing the peak area responses of postextraction bile and urine blank spiked with analyte to those dissolved in methanol at corresponding concentrations [22,23]. The determination of the extraction recovery and matrix effect of IS were similar to that of analytes.…”

Section: Extraction Recovery and Matrix Effectmentioning

confidence: 99%

Simultaneous determination and excretion study of six flavonoids in rat after oral administration ofFructus Sophoraeextract by liquid chromatography tandem mass spectrometry

Zhi¹,

Zhang²,

Li³

et al. 2016

Acta Chromatographica

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Summary.A new, sensitive, and selective high-performance liquid chromatography-tandem mass spectrometric method (HPLC-MS/MS) has been developed for the quantification of six flavonoids (sophoricoside, genistin, genistein, rutin, quercetin, and kaempferol) in rat bile and urine. The sample pretreatment was simple by liquid-liquid extraction. Sulfamethalazole was used as internal standard (IS). During method development, the effect of extraction volume, mobile phase composition, column temperature, and injection volume were varied to optimize sensitivity and achieve a run time as short as possible. Chromatographic separation was accomplished on a C 18 column with a simple linear gradient elution within 9 min. Full validation of the assay was in accordance with the requirement of the validation of the method in vivo and implemented including specificity, linearity, accuracy, precision, recovery, and matrix effect. This is the first report on determination of the major flavones in rat bile and urine after oral administration of Fructus Sophorae extract. The method has been used successfully in excretion studies of six major flavonoids in rat bile and urine.

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“…Plasma was harvested by centrifuging the blood at 2,000 ϫ g for 5 min and stored frozen at Ϫ70°C until analysis. Sample preparation and liquid chromatography-tandem mass spectrometry analyses of pharmacokinetic study samples were done by using the validated method published from our lab (9,24).…”

Section: P-gp Atpase Assaymentioning

confidence: 99%

Investigation of the Functional Role of P-Glycoprotein in Limiting the Oral Bioavailability of Lumefantrine

Wahajuddin

Raju

Singh

et al. 2014

Antimicrob Agents Chemother

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In the quest to explore the reason for the low and variable bioavailability of lumefantrine, we investigated the possible role of P-glycoprotein (P-gp) in lumefantrine intestinal absorption. An in situ single-pass intestinal perfusion study in rats with the P-gp inhibitor verapamil or quinidine and an ATPase assay with human P-gp membranes indicated that lumefantrine is a substrate of P-gp which limits its intestinal absorption. To confirm these findings, an in vivo pharmacokinetic study was performed in rats. The oral administration of verapamil (10 mg/kg of body weight) along with lumefantrine caused a significant increase in its bioavailability with a concomitant decrease in clearance. The increase in bioavailability of lumefantrine could be due to inhibition of P-gp and/or cytochrome P450 3A in the intestine/liver by verapamil. However, in a rat intestinal microsomal stability study, lumefantrine was found to be resistant to oxidative metabolism. Further, an in situ permeation study clearly showed a significant role of P-gp in limiting the oral absorption of lumefantrine. Thus, the increase in lumefantrine bioavailability with verapamil is attributed in part to the P-gp-inhibitory ability of verapamil. In conclusion, lumefantrine is a substrate of P-gp, and active efflux by P-gp across the intestine partly contributed to the low/variable bioavailability of lumefantrine.

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Determination of lumefantrine in rat plasma by liquid–liquid extraction using LC–MS/MS with electrospray ionization: Assay development, validation and application to a pharmacokinetic study

Cited by 39 publications

References 12 publications

Liquid chromatography–mass spectrometry method for the quantification of tamoxifen and its metabolite 4-hydroxytamoxifen in rat plasma: Application to interaction study with biochanin A (an isoflavone)

Liquid chromatography–mass spectrometry method for the quantification of tamoxifen and its metabolite 4-hydroxytamoxifen in rat plasma: Application to interaction study with biochanin A (an isoflavone)

Simultaneous determination and excretion study of six flavonoids in rat after oral administration ofFructus Sophoraeextract by liquid chromatography tandem mass spectrometry

Investigation of the Functional Role of P-Glycoprotein in Limiting the Oral Bioavailability of Lumefantrine

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