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Issue 65, 2018
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An improved HPLC-MS/MS method for simultaneous quantification of propranolol and its two phase I metabolites in plasma of infants with hemangioma and its application to a comparative study of plasma concentrations

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Abstract

Propranolol is now a preferred treatment for infantile hemangioma. However, there are no published papers on the metabolism and concentrations of propranolol in the plasma of infants with hemangioma. In the present study, a sensitive, simple and reliable method was developed and validated for the simultaneous quantification of propranolol and its metabolites 4-hydroxypropranolol (M1) and N-desisopropylpropranolol (M2) in infants' plasma for the first time by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A volume of 100 μL plasma was prepared by one-step protein precipitation with acetonitrile (300 μL), followed by its separation on an Hypersil GOLD C18 column maintained at 40 °C with gradient mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.3 mL min−1. The quantification was performed via multiple reaction monitoring (MRM) by a triple quadrupole mass spectrometer under positive electrospray ionization (ESI) mode. Bisoprolol was chosen as the internal standard. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect and stability. The matrix-matched calibration curves for propranolol ranging from 1 to 500 ng mL−1, for M1 ranging from 0.2 to 100 ng mL−1 and for M2 ranging from 0.2 to 100 ng mL−1 were all linear, with correlation coefficients calculated using weighted (1/x2) least square linear regression analysis. The lower limits of quantification (LLOQs) were 1 ng mL−1, 0.2 ng mL−1 and 0.2 ng mL−1 for propranolol, M1 and M2, respectively. The intra-day and inter-day precisions were less than 7.1% and relative errors were all less than 9.8%. This validated method was successfully applied to quantify the concentrations of propranolol and its metabolites 4-hydroxypropranolol (M1) and N-desisopropylpropranolol (M2) in the plasma of infants with hemangioma after oral administration of different doses of propranolol for the first time.

Graphical abstract: An improved HPLC-MS/MS method for simultaneous quantification of propranolol and its two phase I metabolites in plasma of infants with hemangioma and its application to a comparative study of plasma concentrations

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Publication details

The article was received on 24 Jul 2018, accepted on 17 Oct 2018 and first published on 07 Nov 2018


Article type: Paper
DOI: 10.1039/C8RA06252H
RSC Adv., 2018,8, 37286-37294
  • Open access: Creative Commons BY-NC license
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    An improved HPLC-MS/MS method for simultaneous quantification of propranolol and its two phase I metabolites in plasma of infants with hemangioma and its application to a comparative study of plasma concentrations

    H. He, L. Li, L. Zhao, N. Sun, M. Zhang, Y. Cheng, L. Yu, L. Ma and X. Wang, RSC Adv., 2018, 8, 37286
    DOI: 10.1039/C8RA06252H

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