Validation and application of a 96-well format solid-phase extraction and liquid chromatography–tandem mass spectrometry method for the quantitation of digoxin in human plasma

Hashimoto, Yoshitaka; Shibakawa, Kimio; Nakade, Susumu; Miyata, Yasuyuki

doi:10.1016/j.jchromb.2008.05.026

Cited by 35 publications

(21 citation statements)

References 20 publications

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“…Analytical problems may be also the reason for the lack of data on fecal excretion of digoxin in clinical studies. However, the availability of highly sensitive massspectrometric assays will overcome these limitations in future studies (Hashimoto et al 2008;Kirby et al 2008;Ni et al 2008). Digoxin has low water solubility and high permeability and belong to the Class 2 drugs of the BCS system if the low therapeutic dose and the existence of intestinal uptake transporters for digoxin are ignored (Amidon et al 1995;Lindenberg et al 2004;Shugarts and Benet 2009;Wu and Benet 2005).…”

Section: Limitations Of Digoxinmentioning

confidence: 99%

In Vivo Probes of Drug Transport: Commonly Used Probe Drugs to Assess Function of Intestinal P-glycoprotein (ABCB1) in Humans

Oswald

Terhaag

Siegmund

2010

Handbook of Experimental Pharmacology

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Intestinal P-glycoprotein (P-gp, ABCB1) may significantly influence drug absorption and elimination. Its expression and function is highly variable, regio-selective and influenced by genetic polymorphisms, drug interactions and intestinal diseases. An in vivo probe drug for intestinal P-gp should a registered, safe and well tolerated nonmetabolized selective substrate with low protein binding for which P-gp is rate-limiting during absorption. Other P-gp dependent processes should be of minor influence. The mechanism(s) and kinetics of intestinal uptake must be identified and quantified. Moreover, the release properties of the dosage form should be known. So far, the cardiac glycoside digoxin and the ß₁-selective blocker talinolol have been used in mechanistic clinical studies, because they meet most of these criteria. Digoxin and talinolol are suitable in vivo probe drugs for intestinal P-gp under the precondition, that they are used as tools in carefully designed pharmacokinetic studies with adequate biometrically planning of the sample size and that several limitations are considered in interpreting and discussion of the study results.

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Section: Limitations Of Digoxinmentioning

confidence: 99%

In Vivo Probes of Drug Transport: Commonly Used Probe Drugs to Assess Function of Intestinal P-glycoprotein (ABCB1) in Humans

Oswald

Terhaag

Siegmund

2010

Handbook of Experimental Pharmacology

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“…Liquid-liquid extraction [9][10][11] or solid-phase extraction (SPE) [13][14][15] has been described for the determination of digoxin. We have used liquid-liquid extraction with chloroform-isopropanol (95:5, v/v), the mean extraction efficacies from plasma for digoxin (0.35, 1.96 and 7.80 ng/mL) and IS were found to be (81.7 ± 3.5)%, (85.6 ± 6.9)%, (83.0 ± 3.8)% and (87.2 ± 4.4)%, respectively.…”

Section: Sample Preparationmentioning

confidence: 99%

“…However, the previously published methods require either large plasma volumes or a tandem mass spectrometer. Some methods utilizing solid-phase column extraction were expensive and time-consuming [13][14][15]. In addition, only one recent LC-MS method to determine digoxin in human urine has been published [16].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Development and validation of an LC–MS method with electrospray ionization for quantitation of digoxin in human plasma and urine: Application to a pharmacokinetic study

Shi

Chen

et al. 2008

Journal of Chromatography B

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“…[8] There have also been several papers describing LC-MS/MS methods for digoxin analysis in biological fluids. [9][10][11][12] However, at a total cycle time of more than 4 min per injection, these methods are not suitable for a high-throughput ADME screening environment whereby thousands of samples are generated and analyzed every day. [13,19] To address this challenge and support a high-throughput in vitro P-gp inhibition screen, we developed an ultrafast bioanalytical method for digoxin with a total cycle time of 9 s per injection, using a RapidFire™ 200 system (BIOCIUS Life Sciences, Woburn, MA, USA) with tandem mass spectrometric detection (RF-MS/MS).…”

mentioning

confidence: 99%

Ultrafast mass spectrometry based bioanalytical method for digoxin supporting an in vitro P‐glycoprotein (P‐gp) inhibition screen

Wagner

Kolb

Özbal³

et al. 2011

Rapid Comm Mass Spectrometry

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The evaluation of interactions between drug candidates and transporters such as P-glycoprotein (P-gp) has gained considerable interest in drug discovery and development. Inhibition of P-gp can be assessed by performing bi-directional permeability studies with in vitro P-gp-expressing cellular model systems such as Caco-2 (human colon carcinoma) cells, using digoxin as a substrate probe. Existing methodologies include either assaying (3)H-digoxin with liquid scintillation counting (LSC) detection or assaying non-labeled digoxin with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis at a speed of several minutes per sample. However, it is not feasible to achieve a throughput high enough using these approaches to sustain an early liability screen that generates more than a thousand samples on a daily basis. To address this challenge, we developed an ultrafast (9 s per sample) bioanalytical method for digoxin analysis using RapidFire™, an on-line solid-phase extraction (SPE) system, with MS/MS detection. A stable isotope labeled analog, d3-digoxin, was used as internal standard to minimize potential ionization matrix effect during the RF-MS/MS analysis. The RF-MS/MS method was more than 16 times faster than the LC-MS/MS method but demonstrated similar sensitivity, selectivity, reproducibility, linearity and robustness. P-gp inhibition results of multiple validation compounds obtained with this RF-MS/MS method were in agreement with those generated by both the LC-MS/MS method and the (3)H-radiolabel assay. This method has been successfully deployed to assess P-gp inhibition potential as an important early liability screen for drug-transporter interaction.

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Validation and application of a 96-well format solid-phase extraction and liquid chromatography–tandem mass spectrometry method for the quantitation of digoxin in human plasma

Cited by 35 publications

References 20 publications

In Vivo Probes of Drug Transport: Commonly Used Probe Drugs to Assess Function of Intestinal P-glycoprotein (ABCB1) in Humans

In Vivo Probes of Drug Transport: Commonly Used Probe Drugs to Assess Function of Intestinal P-glycoprotein (ABCB1) in Humans

RETRACTED: Development and validation of an LC–MS method with electrospray ionization for quantitation of digoxin in human plasma and urine: Application to a pharmacokinetic study

Ultrafast mass spectrometry based bioanalytical method for digoxin supporting an in vitro P‐glycoprotein (P‐gp) inhibition screen

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