HPLC-atmospheric pressure chemical ionization mass spectrometric method for enantioselective determination of R,S-propranolol and R,S-hyoscyamine in human plasma

Danuta Siluk, Donald E. Mager, Naomi Gronich, Darrell Abernethy, Irving W. Wainer

Research output: Contribution to journalArticle

Abstract

A method for the simultaneous determination of R- and S-propranolol and R- and S-hyoscyamine in human plasma was developed, validated and applied to the analysis of samples from a clinical study. Sample preparation was performed by solid-phase extraction of 2 ml of human plasma using Oasis MCX cartridges and the enantioselective separations were achieved using a Chirobiotic V chiral stationary phase. The chromatography was carried out using gradient elution with a mobile phase composed of methanol:acetic acid:triethylamine which was varied from 100:0.05:0.04 to 100:0.05:0.1 (v/v/v) over 30 min and delivered at a flow rate 1 ml/min. The internal standard was R,S-propranolol-d7 and the analytes were quantified using a single quadrupole mass spectrometer employing APCI interface operated in the positive ion mode with single ion monitoring. The enantioselective separation factors, α, were 1.15 and 1.07 for S- and R-propranolol and R- and S-hyoscyamine, respectively. The standard curves were linear for all target compounds with coefficients of determination (r2) ranging from 0.9977 to 0.9999. The intra- and inter-day precision and accuracy were ≤13.2% and ≤10.2%, respectively. The assay was used to analyze plasma samples from seven subjects who had received i.v. infusions of R,S-propranolol and R,S-hyoscyamine. The initial data indicate that R-propranolol was eliminated faster than S-propranolol (CL/f = 2.34 ± 0.13 L/kg min vs. 2.07 ± 0.22 L/kg min) and that R-propranolol had a larger volume of distribution at steady-state (Vss/f = 705 ± 165 L/kg vs. 589 ± 130 L/kg). In the case of R,S-hyoscyamine, S-hyoscyamine was eliminated faster than R-hyoscyamine (CL/f = 0.0537 ± 0.0073 L/kg min vs. 0.0439 ± 0.0086 L/kg min), while the volumes of distribution at steady-state were similar for the hyoscyamine enantiomers (Vss/f = 7.82 ± 2.66 L/kg vs. 7.73 ± 1.39 L/kg).

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume859
Issue number2
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

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Hyoscyamine
Plasma (human)
Atmospheric Pressure
Propranolol
Atmospheric pressure
Ionization
High Pressure Liquid Chromatography
Ions
Enantiomers
Solid Phase Extraction
Mass spectrometers
Chromatography
Acetic Acid
Methanol
Assays
Positive ions
Flow rate
Plasmas
Monitoring

Keywords

  • Atropine
  • Chirobiotic V chiral stationary phase
  • LC-APCI-MS
  • Propranolol

ASJC Scopus subject areas

  • Biochemistry

Cite this

HPLC-atmospheric pressure chemical ionization mass spectrometric method for enantioselective determination of R,S-propranolol and R,S-hyoscyamine in human plasma. / Siluk, Danuta; Mager, Donald E.; Gronich, Naomi; Abernethy, Darrell; Wainer, Irving W.

In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 859, No. 2, 15.11.2007, p. 213-221.

Research output: Contribution to journalArticle

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abstract = "A method for the simultaneous determination of R- and S-propranolol and R- and S-hyoscyamine in human plasma was developed, validated and applied to the analysis of samples from a clinical study. Sample preparation was performed by solid-phase extraction of 2 ml of human plasma using Oasis MCX cartridges and the enantioselective separations were achieved using a Chirobiotic V chiral stationary phase. The chromatography was carried out using gradient elution with a mobile phase composed of methanol:acetic acid:triethylamine which was varied from 100:0.05:0.04 to 100:0.05:0.1 (v/v/v) over 30 min and delivered at a flow rate 1 ml/min. The internal standard was R,S-propranolol-d7 and the analytes were quantified using a single quadrupole mass spectrometer employing APCI interface operated in the positive ion mode with single ion monitoring. The enantioselective separation factors, α, were 1.15 and 1.07 for S- and R-propranolol and R- and S-hyoscyamine, respectively. The standard curves were linear for all target compounds with coefficients of determination (r2) ranging from 0.9977 to 0.9999. The intra- and inter-day precision and accuracy were ≤13.2{\%} and ≤10.2{\%}, respectively. The assay was used to analyze plasma samples from seven subjects who had received i.v. infusions of R,S-propranolol and R,S-hyoscyamine. The initial data indicate that R-propranolol was eliminated faster than S-propranolol (CL/f = 2.34 ± 0.13 L/kg min vs. 2.07 ± 0.22 L/kg min) and that R-propranolol had a larger volume of distribution at steady-state (Vss/f = 705 ± 165 L/kg vs. 589 ± 130 L/kg). In the case of R,S-hyoscyamine, S-hyoscyamine was eliminated faster than R-hyoscyamine (CL/f = 0.0537 ± 0.0073 L/kg min vs. 0.0439 ± 0.0086 L/kg min), while the volumes of distribution at steady-state were similar for the hyoscyamine enantiomers (Vss/f = 7.82 ± 2.66 L/kg vs. 7.73 ± 1.39 L/kg).",
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T1 - HPLC-atmospheric pressure chemical ionization mass spectrometric method for enantioselective determination of R,S-propranolol and R,S-hyoscyamine in human plasma

AU - Siluk, Danuta

AU - Mager, Donald E.

AU - Gronich, Naomi

AU - Abernethy, Darrell

AU - Wainer, Irving W.

PY - 2007/11/15

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N2 - A method for the simultaneous determination of R- and S-propranolol and R- and S-hyoscyamine in human plasma was developed, validated and applied to the analysis of samples from a clinical study. Sample preparation was performed by solid-phase extraction of 2 ml of human plasma using Oasis MCX cartridges and the enantioselective separations were achieved using a Chirobiotic V chiral stationary phase. The chromatography was carried out using gradient elution with a mobile phase composed of methanol:acetic acid:triethylamine which was varied from 100:0.05:0.04 to 100:0.05:0.1 (v/v/v) over 30 min and delivered at a flow rate 1 ml/min. The internal standard was R,S-propranolol-d7 and the analytes were quantified using a single quadrupole mass spectrometer employing APCI interface operated in the positive ion mode with single ion monitoring. The enantioselective separation factors, α, were 1.15 and 1.07 for S- and R-propranolol and R- and S-hyoscyamine, respectively. The standard curves were linear for all target compounds with coefficients of determination (r2) ranging from 0.9977 to 0.9999. The intra- and inter-day precision and accuracy were ≤13.2% and ≤10.2%, respectively. The assay was used to analyze plasma samples from seven subjects who had received i.v. infusions of R,S-propranolol and R,S-hyoscyamine. The initial data indicate that R-propranolol was eliminated faster than S-propranolol (CL/f = 2.34 ± 0.13 L/kg min vs. 2.07 ± 0.22 L/kg min) and that R-propranolol had a larger volume of distribution at steady-state (Vss/f = 705 ± 165 L/kg vs. 589 ± 130 L/kg). In the case of R,S-hyoscyamine, S-hyoscyamine was eliminated faster than R-hyoscyamine (CL/f = 0.0537 ± 0.0073 L/kg min vs. 0.0439 ± 0.0086 L/kg min), while the volumes of distribution at steady-state were similar for the hyoscyamine enantiomers (Vss/f = 7.82 ± 2.66 L/kg vs. 7.73 ± 1.39 L/kg).

AB - A method for the simultaneous determination of R- and S-propranolol and R- and S-hyoscyamine in human plasma was developed, validated and applied to the analysis of samples from a clinical study. Sample preparation was performed by solid-phase extraction of 2 ml of human plasma using Oasis MCX cartridges and the enantioselective separations were achieved using a Chirobiotic V chiral stationary phase. The chromatography was carried out using gradient elution with a mobile phase composed of methanol:acetic acid:triethylamine which was varied from 100:0.05:0.04 to 100:0.05:0.1 (v/v/v) over 30 min and delivered at a flow rate 1 ml/min. The internal standard was R,S-propranolol-d7 and the analytes were quantified using a single quadrupole mass spectrometer employing APCI interface operated in the positive ion mode with single ion monitoring. The enantioselective separation factors, α, were 1.15 and 1.07 for S- and R-propranolol and R- and S-hyoscyamine, respectively. The standard curves were linear for all target compounds with coefficients of determination (r2) ranging from 0.9977 to 0.9999. The intra- and inter-day precision and accuracy were ≤13.2% and ≤10.2%, respectively. The assay was used to analyze plasma samples from seven subjects who had received i.v. infusions of R,S-propranolol and R,S-hyoscyamine. The initial data indicate that R-propranolol was eliminated faster than S-propranolol (CL/f = 2.34 ± 0.13 L/kg min vs. 2.07 ± 0.22 L/kg min) and that R-propranolol had a larger volume of distribution at steady-state (Vss/f = 705 ± 165 L/kg vs. 589 ± 130 L/kg). In the case of R,S-hyoscyamine, S-hyoscyamine was eliminated faster than R-hyoscyamine (CL/f = 0.0537 ± 0.0073 L/kg min vs. 0.0439 ± 0.0086 L/kg min), while the volumes of distribution at steady-state were similar for the hyoscyamine enantiomers (Vss/f = 7.82 ± 2.66 L/kg vs. 7.73 ± 1.39 L/kg).

KW - Atropine

KW - Chirobiotic V chiral stationary phase

KW - LC-APCI-MS

KW - Propranolol

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