Ultra-performance liquid chromatography for quantification of amphotericin B plasma concentrations after use of liposomal amphotericin B

Ruth Van Daele; Yvo de Beer; Sander Croes; Rob Aarnoutse; Joost Wauters; Johan Maertens; Isabel Spriet; Roger J. Bruggemann

doi:10.1093/jac/dkaa515

Ultra-performance liquid chromatography for quantification of amphotericin B plasma concentrations after use of liposomal amphotericin B

Ruth Van Daele^*, Yvo de Beer, Sander Croes, Rob Aarnoutse, Joost Wauters, Johan Maertens, Isabel Spriet, Roger J. Bruggemann

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objectives: Liposomal amphotericin B is widely used to treat Life-threatening invasive fungal infections and has replaced conventional amphotericin B deoxycholate due to its more favourable toxicity profile. Despite the fact that Liposomal amphotericin B has been Licensed for several decades, there is still a paucity of clinical pharmacokinetic data. An assay for the quantification of amphotericin B is necessary to allow the study of its pharmacokinetics.

Methods: A UPLC-photodiode array (PDA) analytical method was developed and validated (Linearity, accuracy, precision, dilution integrity, carry-over, selectivity and stability) in accordance with EMA requirements.

Results: The analytical method was validated over a concentration range of 0.5-50.0 mg/L. Accuracy ranged from 97.6% to 112.1% and within-day repeatability and between-day reproducibility from 1.0% to 6.6% and from 0.4% to 4.6%, respectively, dependent on the concentration. Originally, the goal was to develop an analytical method to separate the Liposomal and free amphotericin B fractions, but this was not achieved. Difficulties and bottlenecks encountered are presented.

Conclusions: A UPLC-PDA analytical method was developed to quantify total amphotericin B in plasma after the use of Liposomal amphotericin B.

Original language	English
Pages (from-to)	961-966
Number of pages	6
Journal	Journal of Antimicrobial Chemotherapy
Volume	76
Issue number	4
DOIs	https://doi.org/10.1093/jac/dkaa515
Publication status	Published - Apr 2021

Keywords

PHARMACOKINETICS

Access to Document

10.1093/jac/dkaa515Licence: Free access - publisher

Cite this

@article{60b8a4dd85af4ad2a5ab66d56b573427,

title = "Ultra-performance liquid chromatography for quantification of amphotericin B plasma concentrations after use of liposomal amphotericin B",

abstract = "Objectives: Liposomal amphotericin B is widely used to treat Life-threatening invasive fungal infections and has replaced conventional amphotericin B deoxycholate due to its more favourable toxicity profile. Despite the fact that Liposomal amphotericin B has been Licensed for several decades, there is still a paucity of clinical pharmacokinetic data. An assay for the quantification of amphotericin B is necessary to allow the study of its pharmacokinetics.Methods: A UPLC-photodiode array (PDA) analytical method was developed and validated (Linearity, accuracy, precision, dilution integrity, carry-over, selectivity and stability) in accordance with EMA requirements.Results: The analytical method was validated over a concentration range of 0.5-50.0 mg/L. Accuracy ranged from 97.6% to 112.1% and within-day repeatability and between-day reproducibility from 1.0% to 6.6% and from 0.4% to 4.6%, respectively, dependent on the concentration. Originally, the goal was to develop an analytical method to separate the Liposomal and free amphotericin B fractions, but this was not achieved. Difficulties and bottlenecks encountered are presented.Conclusions: A UPLC-PDA analytical method was developed to quantify total amphotericin B in plasma after the use of Liposomal amphotericin B.",

keywords = "PHARMACOKINETICS",

author = "{Van Daele}, Ruth and {de Beer}, Yvo and Sander Croes and Rob Aarnoutse and Joost Wauters and Johan Maertens and Isabel Spriet and Bruggemann, {Roger J.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.",

year = "2021",

month = apr,

doi = "10.1093/jac/dkaa515",

language = "English",

volume = "76",

pages = "961--966",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Ultra-performance liquid chromatography for quantification of amphotericin B plasma concentrations after use of liposomal amphotericin B

AU - Van Daele, Ruth

AU - de Beer, Yvo

AU - Croes, Sander

AU - Aarnoutse, Rob

AU - Wauters, Joost

AU - Maertens, Johan

AU - Spriet, Isabel

AU - Bruggemann, Roger J.

N1 - Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2021/4

Y1 - 2021/4

N2 - Objectives: Liposomal amphotericin B is widely used to treat Life-threatening invasive fungal infections and has replaced conventional amphotericin B deoxycholate due to its more favourable toxicity profile. Despite the fact that Liposomal amphotericin B has been Licensed for several decades, there is still a paucity of clinical pharmacokinetic data. An assay for the quantification of amphotericin B is necessary to allow the study of its pharmacokinetics.Methods: A UPLC-photodiode array (PDA) analytical method was developed and validated (Linearity, accuracy, precision, dilution integrity, carry-over, selectivity and stability) in accordance with EMA requirements.Results: The analytical method was validated over a concentration range of 0.5-50.0 mg/L. Accuracy ranged from 97.6% to 112.1% and within-day repeatability and between-day reproducibility from 1.0% to 6.6% and from 0.4% to 4.6%, respectively, dependent on the concentration. Originally, the goal was to develop an analytical method to separate the Liposomal and free amphotericin B fractions, but this was not achieved. Difficulties and bottlenecks encountered are presented.Conclusions: A UPLC-PDA analytical method was developed to quantify total amphotericin B in plasma after the use of Liposomal amphotericin B.

AB - Objectives: Liposomal amphotericin B is widely used to treat Life-threatening invasive fungal infections and has replaced conventional amphotericin B deoxycholate due to its more favourable toxicity profile. Despite the fact that Liposomal amphotericin B has been Licensed for several decades, there is still a paucity of clinical pharmacokinetic data. An assay for the quantification of amphotericin B is necessary to allow the study of its pharmacokinetics.Methods: A UPLC-photodiode array (PDA) analytical method was developed and validated (Linearity, accuracy, precision, dilution integrity, carry-over, selectivity and stability) in accordance with EMA requirements.Results: The analytical method was validated over a concentration range of 0.5-50.0 mg/L. Accuracy ranged from 97.6% to 112.1% and within-day repeatability and between-day reproducibility from 1.0% to 6.6% and from 0.4% to 4.6%, respectively, dependent on the concentration. Originally, the goal was to develop an analytical method to separate the Liposomal and free amphotericin B fractions, but this was not achieved. Difficulties and bottlenecks encountered are presented.Conclusions: A UPLC-PDA analytical method was developed to quantify total amphotericin B in plasma after the use of Liposomal amphotericin B.

KW - PHARMACOKINETICS

U2 - 10.1093/jac/dkaa515

DO - 10.1093/jac/dkaa515

M3 - Article

C2 - 33351897

SN - 0305-7453

VL - 76

SP - 961

EP - 966

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 4

ER -