A sensitive validated LC-MS/MS method for quantification of itraconazole in human plasma for pharmacokinetic and bioequivalence study in 24 Korean volunteers

Si Youn Rhim, Jin Hee Park, Yoo Sin Park, Dong Sun Kim, Min Ho Lee, Leslie M. Shaw, Ju Seop Kang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

A rapid and highly sensitive liquid chromatography/ electrospray ionization tandem mass spectrometric method (LC/ESI-MS/MS) for itraconazole determination in human plasma was validated and applied to pharmacokinetic and bioequivalence study in humans. In a randomized crossover design with a 1-week period, each subject received a 200 mg itraconazole capsule. The analytical procedures involved a less time-consuming, simple protein precipitation with methyl t-butyl ether and separation by HPLC. The ionization was optimized using electrospray ionization (ESI) with positive ion mode and selectivity was achieved by MS/MS analysis, m/z 705.3 → 392.4 and m/z 374.3 → 141.0 for itraconazole and internal standard (IS), respectively. The standard calibration curves showed good linearity within the range of 1 (LLOQ) to 500 ng/mL for itraconazole in human plasma with a correlation coefficient r ≥ 0.9952. The retention times of itraconazole (0.9 min) and IS (0.84 min) suggest the high throughput of the proposed method. No significant metabolic compounds were found to interfere with the analysis. The coefficient of variation values of both intra- and inter-day were below 13.7% and 10.9%, respectively. Intra- and inter-day accuracies were 95.6-108.2% and 86.6-117.5%, respectively. This method was successfully applied for pharmacokinetic and bioequivalence study in 24 healthy human subjects by analysis of blood samples taken up to 72 h after an oral dose of 200 mg of itraconazole.

Original languageEnglish
Pages (from-to)71-75
Number of pages5
JournalPharmazie
Volume64
Issue number2
DOIs
StatePublished - 2009 Feb 1

Fingerprint

Therapeutic Equivalency
Itraconazole
Volunteers
Pharmacokinetics
Liquid Chromatography
Cross-Over Studies
Calibration
Capsules
Healthy Volunteers
High Pressure Liquid Chromatography
Ions
Proteins

Cite this

@article{a20069cd112c4cbd850aaefb5174b038,
title = "A sensitive validated LC-MS/MS method for quantification of itraconazole in human plasma for pharmacokinetic and bioequivalence study in 24 Korean volunteers",
abstract = "A rapid and highly sensitive liquid chromatography/ electrospray ionization tandem mass spectrometric method (LC/ESI-MS/MS) for itraconazole determination in human plasma was validated and applied to pharmacokinetic and bioequivalence study in humans. In a randomized crossover design with a 1-week period, each subject received a 200 mg itraconazole capsule. The analytical procedures involved a less time-consuming, simple protein precipitation with methyl t-butyl ether and separation by HPLC. The ionization was optimized using electrospray ionization (ESI) with positive ion mode and selectivity was achieved by MS/MS analysis, m/z 705.3 → 392.4 and m/z 374.3 → 141.0 for itraconazole and internal standard (IS), respectively. The standard calibration curves showed good linearity within the range of 1 (LLOQ) to 500 ng/mL for itraconazole in human plasma with a correlation coefficient r ≥ 0.9952. The retention times of itraconazole (0.9 min) and IS (0.84 min) suggest the high throughput of the proposed method. No significant metabolic compounds were found to interfere with the analysis. The coefficient of variation values of both intra- and inter-day were below 13.7{\%} and 10.9{\%}, respectively. Intra- and inter-day accuracies were 95.6-108.2{\%} and 86.6-117.5{\%}, respectively. This method was successfully applied for pharmacokinetic and bioequivalence study in 24 healthy human subjects by analysis of blood samples taken up to 72 h after an oral dose of 200 mg of itraconazole.",
author = "Rhim, {Si Youn} and Park, {Jin Hee} and Park, {Yoo Sin} and Kim, {Dong Sun} and Lee, {Min Ho} and Shaw, {Leslie M.} and Kang, {Ju Seop}",
year = "2009",
month = "2",
day = "1",
doi = "10.1691/ph.2009.7795",
language = "English",
volume = "64",
pages = "71--75",
journal = "Pharmazie",
issn = "0031-7144",
number = "2",

}

A sensitive validated LC-MS/MS method for quantification of itraconazole in human plasma for pharmacokinetic and bioequivalence study in 24 Korean volunteers. / Rhim, Si Youn; Park, Jin Hee; Park, Yoo Sin; Kim, Dong Sun; Lee, Min Ho; Shaw, Leslie M.; Kang, Ju Seop.

In: Pharmazie, Vol. 64, No. 2, 01.02.2009, p. 71-75.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A sensitive validated LC-MS/MS method for quantification of itraconazole in human plasma for pharmacokinetic and bioequivalence study in 24 Korean volunteers

AU - Rhim, Si Youn

AU - Park, Jin Hee

AU - Park, Yoo Sin

AU - Kim, Dong Sun

AU - Lee, Min Ho

AU - Shaw, Leslie M.

AU - Kang, Ju Seop

PY - 2009/2/1

Y1 - 2009/2/1

N2 - A rapid and highly sensitive liquid chromatography/ electrospray ionization tandem mass spectrometric method (LC/ESI-MS/MS) for itraconazole determination in human plasma was validated and applied to pharmacokinetic and bioequivalence study in humans. In a randomized crossover design with a 1-week period, each subject received a 200 mg itraconazole capsule. The analytical procedures involved a less time-consuming, simple protein precipitation with methyl t-butyl ether and separation by HPLC. The ionization was optimized using electrospray ionization (ESI) with positive ion mode and selectivity was achieved by MS/MS analysis, m/z 705.3 → 392.4 and m/z 374.3 → 141.0 for itraconazole and internal standard (IS), respectively. The standard calibration curves showed good linearity within the range of 1 (LLOQ) to 500 ng/mL for itraconazole in human plasma with a correlation coefficient r ≥ 0.9952. The retention times of itraconazole (0.9 min) and IS (0.84 min) suggest the high throughput of the proposed method. No significant metabolic compounds were found to interfere with the analysis. The coefficient of variation values of both intra- and inter-day were below 13.7% and 10.9%, respectively. Intra- and inter-day accuracies were 95.6-108.2% and 86.6-117.5%, respectively. This method was successfully applied for pharmacokinetic and bioequivalence study in 24 healthy human subjects by analysis of blood samples taken up to 72 h after an oral dose of 200 mg of itraconazole.

AB - A rapid and highly sensitive liquid chromatography/ electrospray ionization tandem mass spectrometric method (LC/ESI-MS/MS) for itraconazole determination in human plasma was validated and applied to pharmacokinetic and bioequivalence study in humans. In a randomized crossover design with a 1-week period, each subject received a 200 mg itraconazole capsule. The analytical procedures involved a less time-consuming, simple protein precipitation with methyl t-butyl ether and separation by HPLC. The ionization was optimized using electrospray ionization (ESI) with positive ion mode and selectivity was achieved by MS/MS analysis, m/z 705.3 → 392.4 and m/z 374.3 → 141.0 for itraconazole and internal standard (IS), respectively. The standard calibration curves showed good linearity within the range of 1 (LLOQ) to 500 ng/mL for itraconazole in human plasma with a correlation coefficient r ≥ 0.9952. The retention times of itraconazole (0.9 min) and IS (0.84 min) suggest the high throughput of the proposed method. No significant metabolic compounds were found to interfere with the analysis. The coefficient of variation values of both intra- and inter-day were below 13.7% and 10.9%, respectively. Intra- and inter-day accuracies were 95.6-108.2% and 86.6-117.5%, respectively. This method was successfully applied for pharmacokinetic and bioequivalence study in 24 healthy human subjects by analysis of blood samples taken up to 72 h after an oral dose of 200 mg of itraconazole.

UR - http://www.scopus.com/inward/record.url?scp=65349097331&partnerID=8YFLogxK

U2 - 10.1691/ph.2009.7795

DO - 10.1691/ph.2009.7795

M3 - Article

C2 - 19320276

AN - SCOPUS:65349097331

VL - 64

SP - 71

EP - 75

JO - Pharmazie

JF - Pharmazie

SN - 0031-7144

IS - 2

ER -