Quantitation of pilsicainide in microscale samples of human biological fluids using liquid chromatography-tandem mass spectrometry

Mikiko Shimizu, Masayuki Hashiguchi, Tsuyoshi Shiga, Koichi Nakamura, Hiroomi Tamura, Mayumi Mochizuki

Research output: Contribution to journalArticle

Abstract

This paper describes a sensitive, reliable method to determine pilsicainide (PLC) levels in microscale sample volumes of human biological fluids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). PLC and quinidine as an internal standard were extracted with diethylether from 0.1. mL of alkalinized biological fluids. The extract was injected into an analytical column (l-column 2 ODS, 75. mm. ×. 2.1. mm i.d.). The mobile phase for separation consisted of 5. mM ammonium acetate (pH 4.5)/methanol (4:1, v/v) and was delivered at a flow rate of 0.2. mL/min. The drift voltage was 100. V. The sampling aperture was heated at 120. °C and the shield temperature was 260. °C. The ion transitions used to monitor analytes were m/. z 273. →. m/. z 110 for PLC and m/. z 325. →. m/. z 79 for quinidine. The total time for chromatographic separation was less than 8. min. The validated concentration ranges of this method for PLC were 5-2000. ng/mL in plasma, 5-500. ng/mL in ultrafiltered plasma solution, and 25-2000. ng/mL in urine. Mean recoveries of PLC in plasma, ultrafiltered plasma solution, and urine were 93.2-99.7%, 91.4-100.6%, and 93.9-104.7%, respectively. Intra- and interday coefficients of variation for PLC were less than 6.0% and 4.3% in plasma, 6.1% and 3.7% in ultrafiltered plasma solution, and 5.4% and 2.5% in urine at the above concentration ranges, respectively. The lower limit of quantification for PLC in plasma, ultrafiltered plasma solution, and urine were 5. ng/mL, 5. ng/mL, and 25. ng/mL, respectively. This method can be applied to pharmacokinetic study and therapeutic drug monitoring in special populations such as neonates, infants, and the elderly by making effective use of residual samples used for general clinical laboratory testing.

Original languageEnglish
Pages (from-to)172-179
Number of pages8
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume985
DOIs
Publication statusPublished - 2015 Mar 5

Fingerprint

Liquid chromatography
Tandem Mass Spectrometry
Liquid Chromatography
Mass spectrometry
Plasmas
Fluids
Urine
Quinidine
Clinical laboratories
Electrospray ionization
Pharmacokinetics
pilsicainide
Drug Monitoring
Methanol
Flow rate
Newborn Infant
Ions
Sampling
Recovery
Temperature

Keywords

  • LC-MS/MS
  • Pharmacokinetics
  • Pilsicainide
  • Plasma
  • Therapeutic drug monitoring
  • Urine

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry
  • Cell Biology
  • Clinical Biochemistry

Cite this

@article{bbaecb4b78f44a45892d7ecf1d4b92c2,
title = "Quantitation of pilsicainide in microscale samples of human biological fluids using liquid chromatography-tandem mass spectrometry",
abstract = "This paper describes a sensitive, reliable method to determine pilsicainide (PLC) levels in microscale sample volumes of human biological fluids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). PLC and quinidine as an internal standard were extracted with diethylether from 0.1. mL of alkalinized biological fluids. The extract was injected into an analytical column (l-column 2 ODS, 75. mm. ×. 2.1. mm i.d.). The mobile phase for separation consisted of 5. mM ammonium acetate (pH 4.5)/methanol (4:1, v/v) and was delivered at a flow rate of 0.2. mL/min. The drift voltage was 100. V. The sampling aperture was heated at 120. °C and the shield temperature was 260. °C. The ion transitions used to monitor analytes were m/. z 273. →. m/. z 110 for PLC and m/. z 325. →. m/. z 79 for quinidine. The total time for chromatographic separation was less than 8. min. The validated concentration ranges of this method for PLC were 5-2000. ng/mL in plasma, 5-500. ng/mL in ultrafiltered plasma solution, and 25-2000. ng/mL in urine. Mean recoveries of PLC in plasma, ultrafiltered plasma solution, and urine were 93.2-99.7{\%}, 91.4-100.6{\%}, and 93.9-104.7{\%}, respectively. Intra- and interday coefficients of variation for PLC were less than 6.0{\%} and 4.3{\%} in plasma, 6.1{\%} and 3.7{\%} in ultrafiltered plasma solution, and 5.4{\%} and 2.5{\%} in urine at the above concentration ranges, respectively. The lower limit of quantification for PLC in plasma, ultrafiltered plasma solution, and urine were 5. ng/mL, 5. ng/mL, and 25. ng/mL, respectively. This method can be applied to pharmacokinetic study and therapeutic drug monitoring in special populations such as neonates, infants, and the elderly by making effective use of residual samples used for general clinical laboratory testing.",
keywords = "LC-MS/MS, Pharmacokinetics, Pilsicainide, Plasma, Therapeutic drug monitoring, Urine",
author = "Mikiko Shimizu and Masayuki Hashiguchi and Tsuyoshi Shiga and Koichi Nakamura and Hiroomi Tamura and Mayumi Mochizuki",
year = "2015",
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TY - JOUR

T1 - Quantitation of pilsicainide in microscale samples of human biological fluids using liquid chromatography-tandem mass spectrometry

AU - Shimizu, Mikiko

AU - Hashiguchi, Masayuki

AU - Shiga, Tsuyoshi

AU - Nakamura, Koichi

AU - Tamura, Hiroomi

AU - Mochizuki, Mayumi

PY - 2015/3/5

Y1 - 2015/3/5

N2 - This paper describes a sensitive, reliable method to determine pilsicainide (PLC) levels in microscale sample volumes of human biological fluids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). PLC and quinidine as an internal standard were extracted with diethylether from 0.1. mL of alkalinized biological fluids. The extract was injected into an analytical column (l-column 2 ODS, 75. mm. ×. 2.1. mm i.d.). The mobile phase for separation consisted of 5. mM ammonium acetate (pH 4.5)/methanol (4:1, v/v) and was delivered at a flow rate of 0.2. mL/min. The drift voltage was 100. V. The sampling aperture was heated at 120. °C and the shield temperature was 260. °C. The ion transitions used to monitor analytes were m/. z 273. →. m/. z 110 for PLC and m/. z 325. →. m/. z 79 for quinidine. The total time for chromatographic separation was less than 8. min. The validated concentration ranges of this method for PLC were 5-2000. ng/mL in plasma, 5-500. ng/mL in ultrafiltered plasma solution, and 25-2000. ng/mL in urine. Mean recoveries of PLC in plasma, ultrafiltered plasma solution, and urine were 93.2-99.7%, 91.4-100.6%, and 93.9-104.7%, respectively. Intra- and interday coefficients of variation for PLC were less than 6.0% and 4.3% in plasma, 6.1% and 3.7% in ultrafiltered plasma solution, and 5.4% and 2.5% in urine at the above concentration ranges, respectively. The lower limit of quantification for PLC in plasma, ultrafiltered plasma solution, and urine were 5. ng/mL, 5. ng/mL, and 25. ng/mL, respectively. This method can be applied to pharmacokinetic study and therapeutic drug monitoring in special populations such as neonates, infants, and the elderly by making effective use of residual samples used for general clinical laboratory testing.

AB - This paper describes a sensitive, reliable method to determine pilsicainide (PLC) levels in microscale sample volumes of human biological fluids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). PLC and quinidine as an internal standard were extracted with diethylether from 0.1. mL of alkalinized biological fluids. The extract was injected into an analytical column (l-column 2 ODS, 75. mm. ×. 2.1. mm i.d.). The mobile phase for separation consisted of 5. mM ammonium acetate (pH 4.5)/methanol (4:1, v/v) and was delivered at a flow rate of 0.2. mL/min. The drift voltage was 100. V. The sampling aperture was heated at 120. °C and the shield temperature was 260. °C. The ion transitions used to monitor analytes were m/. z 273. →. m/. z 110 for PLC and m/. z 325. →. m/. z 79 for quinidine. The total time for chromatographic separation was less than 8. min. The validated concentration ranges of this method for PLC were 5-2000. ng/mL in plasma, 5-500. ng/mL in ultrafiltered plasma solution, and 25-2000. ng/mL in urine. Mean recoveries of PLC in plasma, ultrafiltered plasma solution, and urine were 93.2-99.7%, 91.4-100.6%, and 93.9-104.7%, respectively. Intra- and interday coefficients of variation for PLC were less than 6.0% and 4.3% in plasma, 6.1% and 3.7% in ultrafiltered plasma solution, and 5.4% and 2.5% in urine at the above concentration ranges, respectively. The lower limit of quantification for PLC in plasma, ultrafiltered plasma solution, and urine were 5. ng/mL, 5. ng/mL, and 25. ng/mL, respectively. This method can be applied to pharmacokinetic study and therapeutic drug monitoring in special populations such as neonates, infants, and the elderly by making effective use of residual samples used for general clinical laboratory testing.

KW - LC-MS/MS

KW - Pharmacokinetics

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KW - Plasma

KW - Therapeutic drug monitoring

KW - Urine

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U2 - 10.1016/j.jchromb.2015.01.013

DO - 10.1016/j.jchromb.2015.01.013

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VL - 985

SP - 172

EP - 179

JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

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SN - 1570-0232

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