Sampling only ten microliters of whole blood for the quantification of poorly soluble drugs: Itraconazole as case study

Thiry, Justine; Évrard, Brigitte; Nys, Gwenaël; Fillet, Marianne; Kok, Miranda

doi:10.1016/j.chroma.2016.12.009

Cited by 27 publications

(17 citation statements)

References 30 publications

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“…The hydrophilic tip is found at the end of a plastic handler that can be attached to automated sample processing systems. VAMS is successfully used today for pharmacokinetic and therapeutic drug monitoring studies both in animal and human experiments [15,16]. VAMS devices were created for their ability of remote blood sampling, easy transportation of collected dried blood samples without using special transportation equipment such as cold packs or dried ice, assuring analyte stability.…”

Section: Introductionmentioning

confidence: 99%

Determination of iohexol by capillary blood microsampling and UHPLC-MS/MS

Ion

Legoff

Cavalier

et al. 2019

Journal of Pharmaceutical Analysis

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One of the most important tools used to evaluate kidney function in the context of chronic kidney disease or other renal function related pathologies is the exploration of glomerular filtration rate (GFR). Iohexol is up to this moment a good candidate molecule for the GFR assessment since it exhibits minimum protein binding rates and minimum extra-renal clearance, being neither secreted nor reabsorbed at the tubular level. This study proposes and evaluates a new LC-MS/MS method for the iohexol determination from capillary blood, prelevated using volumetric absorbative microsampling (VAMS) systems. As an alternative to VAMS, a brand new HemaPEN ® device for micro-prelevation was also tested. A new high throughput sample preparation protocol adapted for iohexol quantification from whole blood VAMS samples was developed. The medium term stability study of iohexol in dried whole blood VAMS samples that was conducted showed a good stability of this molecule for up to 12 days. By collecting only 10 μL of blood, iohexol can be analyzed from dried whole blood VAMS samples for concentration ranges between 1 and 250 μg/mL. Due to the analyte stability in VAMS for up to 12 days, this approach might be successfully applied for GFR assessment for clinical cases allowing minimum invasiveness and even delayed analysis.

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Section: Introductionmentioning

confidence: 99%

Determination of iohexol by capillary blood microsampling and UHPLC-MS/MS

Ion

Legoff

Cavalier

et al. 2019

Journal of Pharmaceutical Analysis

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“…The Three Rs rule—replacement, reduction, and refinement—is a set of guiding principles for the more ethical use of animals in scientific study. Nowadays, complying with this rule is of utmost importance, and efforts must be made to enhance animal welfare (Thiry, Evrard, Nys, Fillet, & Kok, 2017). In this study, 20 μL of plasma was needed for sample preparation.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic and bioavailability study of 5‐hydroxy‐4‐methoxycanthin‐6‐one, a typical canthinone alkaloid, in rats using ultra‐high performance liquid chromatography/electrospray ionization tandem mass spectrometry

Zhao

Guo³

et al. 2020

Biomedical Chromatography

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5‐methoxycanthin‐6‐one, a major canthinone alkaloid isolated from Picrasma quassioides, exhibited significant pharmacological activities. In this study, a rapid and sensitive LC–MS/MS method was established and validated for the determination of 5‐hydroxy‐4‐methoxycanthin‐6‐one in rat plasma. Small quantities (20 μL) of plasma sample were used for sample preparation. 5‐Hydroxy‐4‐methoxycanthin‐6‐one and an internal standard (IS, caffeine) were separated using an ACQUITY HSS T3 column (50 × 2.1 mm, 1.7 μm; Waters, Milford, MA, USA). The mobile phase was composed of 0.1% formic acid in water and acetonitrile. Precursor‐to‐product ion transitions were m/z 267.0 → 168.2 and m/z 195.0 → 138.1 for quantitative monitoring of 5‐hydroxy‐4‐methoxycanthin‐6‐one and IS, respectively. The assay was linear over the concentration range of 0.5–500 ng/mL (r > 0.99) with the lower limit of quantification 0.5 ng/mL. Other parameters, including intra‐ and inter‐day precision and accuracy, carryover, stability, extraction recovery, matrix effect, and dilution effect, were within acceptable limits. The validated method was successfully applied to pharmacokinetic study in rats after intravenous (5 mg/kg) and oral (10, 25, 50 mg/kg) administration of 5‐hydroxy‐4‐methoxycanthin‐6‐one. The result indicated that 5‐hydroxy‐4‐methoxycanthin‐6‐one was quickly absorbed into the blood and reached the highest concentration at ~33.0–42.0 min, with moderate elimination half‐life (0.85–2.11 h) and low bioavailability (16.62–24.42%) after oral administration. The study provided valuable information that can be used as a reference for studying other canthinone alkaloids.

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“…Quantification of itraconazole was possible by using only 10 μL of whole blood: the itraconazole was slightly affected by the matrix (91.2%), whereas there were slightly positive MEs observed for hydroxy-itraconazole (110.7%) [ 108 ]. When the sample dilution approach or injection of smaller volumes does not provide adequate solutions for overcoming MEs, sample preparation becomes compulsory to selectively eliminate or reduce co-eluting interferences.…”

Section: Minimizing Matrix Effectsmentioning

confidence: 99%

Compensate for or Minimize Matrix Effects? Strategies for Overcoming Matrix Effects in Liquid Chromatography-Mass Spectrometry Technique: A Tutorial Review

et al. 2020

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In recent decades, mass spectrometry techniques, particularly when combined with separation methods such as high-performance liquid chromatography, have become increasingly important in pharmaceutical, bio-analytical, environmental, and food science applications because they afford high selectivity and sensitivity. However, mass spectrometry has limitations due to the matrix effects (ME), which can be particularly marked in complex mixes, when the analyte co-elutes together with other molecules, altering analysis results quantitatively. This may be detrimental during method validation, negatively affecting reproducibility, linearity, selectivity, accuracy, and sensitivity. Starting from literature and own experience, this review intends to provide a simple guideline for selecting the best operative conditions to overcome matrix effects in LC-MS techniques, to obtain the best result in the shortest time. The proposed methodology can be of benefit in different sectors, such as pharmaceutical, bio-analytical, environmental, and food sciences. Depending on the required sensitivity, analysts may minimize or compensate for ME. When sensitivity is crucial, analysis must try to minimize ME by adjusting MS parameters, chromatographic conditions, or optimizing clean-up. On the contrary, to compensate for ME analysts should have recourse to calibration approaches depending on the availability of blank matrix. When blank matrices are available, calibration can occur through isotope labeled internal standards and matrix matched calibration standards; conversely, when blank matrices are not available, calibration can be performed through isotope labeled internal standards, background subtraction, or surrogate matrices. In any case, an adjusting of MS parameters, chromatographic conditions, or a clean-up are necessary.

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Sampling only ten microliters of whole blood for the quantification of poorly soluble drugs: Itraconazole as case study

Cited by 27 publications

References 30 publications

Determination of iohexol by capillary blood microsampling and UHPLC-MS/MS

Determination of iohexol by capillary blood microsampling and UHPLC-MS/MS

Pharmacokinetic and bioavailability study of 5‐hydroxy‐4‐methoxycanthin‐6‐one, a typical canthinone alkaloid, in rats using ultra‐high performance liquid chromatography/electrospray ionization tandem mass spectrometry

Compensate for or Minimize Matrix Effects? Strategies for Overcoming Matrix Effects in Liquid Chromatography-Mass Spectrometry Technique: A Tutorial Review

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