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Determination of picropodophyllin and its isomer podophyllotoxin in human serum samples with electrospray ionization of hexylamine adducts by liquid chromatography-tandem mass spectrometry.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Feb 15; 879(5-6):326-34.JC

Abstract

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of the new anticancer agent picropodophyllin (AXL1717) and its isomer podophyllotoxin levels in human serum has been developed. Monitoring of hexylamine adducts rather than proton adducts was used to optimize sensitivity. The chromatography system was an Acquity BEH C18, 2.1 mm × 50 mm 1.7 μm column with gradient elution (mobile phase A: 2.5 mM hexylamine and 5 mM formic acid in Milli-Q water and mobile phase B: methanol). The retention times were 1.4 min for picropodophyllin, 1.5 min for podophyllotoxin and 1.9 min for internal standard deoxypodophyllotoxin. The isomers were base-line separated. The analytes were detected after electrospray ionization in positive mode with selected reaction monitoring (SRM) with ion transitions m/z 516→102 for picropodophyllin and podophyllotoxin and m/z 500→102 for internal standard. The sample preparation was protein precipitation with acetonitrile (1:3) containing internal standard followed by dilution of the supernatant with mobile phase A (1:1). The limit of quantification (LOQ) was 0.01 μmol/L for picropodophyllin and podophyllotoxin. The limit of detection (LOD) at 3 times the signal to noise (S/N) was estimated below 0.001 μmol/L for picropodophyllin and podophyllotoxin. The quantification range of the method was between 0.01 μmol/L and 5 μmol/L for both isomers. The accuracy was within ±15% of the theoretical value for both picropodophyllin and podophyllotoxin and inter-assay precision did not exceed ±15%, except for the 0.016 μmol/L level of podophyllotoxin, which was 18%. The selectivity of the method was verified by analysis of two different product ions for each analyte and by analysis for interference of seven different batches of blank human serum. The combined recovery and matrix effects were about 83% for picropodophyllin and podophyllotoxin. The new LC-MS/MS method showed sufficient sensitivity and selectivity for determination of picropodophyllin and its isomer podophyllotoxin levels in human serum from subjects receiving therapeutic doses of AXL1717.

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Authors+Show Affiliations

Rönquist-Nii Y
Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden. yuko.ronquist@karolinska.se
Eksborg S
No affiliation info available
Axelson M
No affiliation info available
Harmenberg J
No affiliation info available
Ekman S
No affiliation info available
Bergqvist M
No affiliation info available
Beck O
No affiliation info available

MeSH

AdultAged, 80 and overAminesAnimalsChromatography, LiquidDrug StabilityDrugs, Chinese HerbalFemaleHumansLeast-Squares AnalysisMaleMicePodophyllotoxinReproducibility of ResultsSensitivity and SpecificitySpectrometry, Mass, Electrospray IonizationSwineTandem Mass Spectrometry

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21251888

Citation

Rönquist-Nii, Yuko, et al. "Determination of Picropodophyllin and Its Isomer Podophyllotoxin in Human Serum Samples With Electrospray Ionization of Hexylamine Adducts By Liquid Chromatography-tandem Mass Spectrometry." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 879, no. 5-6, 2011, pp. 326-34.
Rönquist-Nii Y, Eksborg S, Axelson M, et al. Determination of picropodophyllin and its isomer podophyllotoxin in human serum samples with electrospray ionization of hexylamine adducts by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2011;879(5-6):326-34.
Rönquist-Nii, Y., Eksborg, S., Axelson, M., Harmenberg, J., Ekman, S., Bergqvist, M., & Beck, O. (2011). Determination of picropodophyllin and its isomer podophyllotoxin in human serum samples with electrospray ionization of hexylamine adducts by liquid chromatography-tandem mass spectrometry. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 879(5-6), 326-34. https://doi.org/10.1016/j.jchromb.2010.12.017
Rönquist-Nii Y, et al. Determination of Picropodophyllin and Its Isomer Podophyllotoxin in Human Serum Samples With Electrospray Ionization of Hexylamine Adducts By Liquid Chromatography-tandem Mass Spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Feb 15;879(5-6):326-34. PubMed PMID: 21251888.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Determination of picropodophyllin and its isomer podophyllotoxin in human serum samples with electrospray ionization of hexylamine adducts by liquid chromatography-tandem mass spectrometry. AU - Rönquist-Nii,Yuko, AU - Eksborg,Staffan, AU - Axelson,Magnus, AU - Harmenberg,Johan, AU - Ekman,Simon, AU - Bergqvist,Michael, AU - Beck,Olof, Y1 - 2010/12/28/ PY - 2010/07/16/received PY - 2010/12/10/revised PY - 2010/12/17/accepted PY - 2011/1/22/entrez PY - 2011/1/22/pubmed PY - 2011/6/4/medline SP - 326 EP - 34 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J Chromatogr B Analyt Technol Biomed Life Sci VL - 879 IS - 5-6 N2 - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of the new anticancer agent picropodophyllin (AXL1717) and its isomer podophyllotoxin levels in human serum has been developed. Monitoring of hexylamine adducts rather than proton adducts was used to optimize sensitivity. The chromatography system was an Acquity BEH C18, 2.1 mm × 50 mm 1.7 μm column with gradient elution (mobile phase A: 2.5 mM hexylamine and 5 mM formic acid in Milli-Q water and mobile phase B: methanol). The retention times were 1.4 min for picropodophyllin, 1.5 min for podophyllotoxin and 1.9 min for internal standard deoxypodophyllotoxin. The isomers were base-line separated. The analytes were detected after electrospray ionization in positive mode with selected reaction monitoring (SRM) with ion transitions m/z 516→102 for picropodophyllin and podophyllotoxin and m/z 500→102 for internal standard. The sample preparation was protein precipitation with acetonitrile (1:3) containing internal standard followed by dilution of the supernatant with mobile phase A (1:1). The limit of quantification (LOQ) was 0.01 μmol/L for picropodophyllin and podophyllotoxin. The limit of detection (LOD) at 3 times the signal to noise (S/N) was estimated below 0.001 μmol/L for picropodophyllin and podophyllotoxin. The quantification range of the method was between 0.01 μmol/L and 5 μmol/L for both isomers. The accuracy was within ±15% of the theoretical value for both picropodophyllin and podophyllotoxin and inter-assay precision did not exceed ±15%, except for the 0.016 μmol/L level of podophyllotoxin, which was 18%. The selectivity of the method was verified by analysis of two different product ions for each analyte and by analysis for interference of seven different batches of blank human serum. The combined recovery and matrix effects were about 83% for picropodophyllin and podophyllotoxin. The new LC-MS/MS method showed sufficient sensitivity and selectivity for determination of picropodophyllin and its isomer podophyllotoxin levels in human serum from subjects receiving therapeutic doses of AXL1717. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/21251888/Determination_of_picropodophyllin_and_its_isomer_podophyllotoxin_in_human_serum_samples_with_electrospray_ionization_of_hexylamine_adducts_by_liquid_chromatography_tandem_mass_spectrometry_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(10)00773-7 DB - PRIME DP - Unbound Medicine ER -