Development, validation and application of a novel liquid chromatography tandem mass spectrometry assay measuring uracil, 5,6-dihydrouracil, 5-fluorouracil, 5,6-dihydro-5-fluorouracil, α-fluoro-β-ureidopropionic acid and α-fluoro-β-alanine in human plasma

Abstract:

:The plasma 5,6-dihydrouracil/uracil (UH2/U) ratio is a possible phenotypic marker of dihydropyrimidine dehydrogenase (DPD) activity, hence an index of 5-fluorouracil (5-FU) response and toxicity. Studies have re-affirmed the value of 5-FU and 5,6-dihydro-5-fluorouracil (FUH2) for therapeutic drug monitoring (TDM). However, FUH2 has limited stability in plasma, necessitating expedited plasma separation and freezing, where routine compliance may not be easy. The metabolites α-fluoro-β-ureidopropionic acid (FUPA) and α-fluoro-β-alanine (FβAL) are stable in plasma and are probable candidates for TDM. This paper describes development, validation and application of an LC-MS/MS assay quantifying U, UH2, 5-FU, FUH2, FUPA and FβAL in human plasma. Extraction was by salt-assisted liquid-liquid extraction (LLE) in two-stages with pH adjustment. The supernatants were mixed, dried and reconstituted. Analytes were resolved on the Luna PFP (2) (150×2.00mm, 3μ) column by gradient elution and analyzed by tandem mass spectrometry via electrospray ionisation in positive polarity. The analytical response was linear (r2≥0.99) in the concentration (ng/mL) ranges: 50-10 000 for FβAL and FUH2, 50-5 000 for FUPA, 50-100 000 for 5-FU, 5-200 for U and 10-400 for UH2. Within- and between-run accuracy and precision were ≤ 10.2% and ≤ 9.8% respectively across the QC range and inclusive of LLOQ. The internal standard (IS) normalised matrix effects were within 93-112% with CV of ≤ 9.7% and normalised recoveries were within 91-107% with CV of ≤ 9.8%. This robust assay was successfully applied to samples from rectal and colorectal cancer patients (n=10) on 5-FU. Deviations ≤ 2.0% from the mean values were observed when incurred samples were reanalysed.

journal_name

J Pharm Biomed Anal

authors

Chavani O,Jensen BP,Strother RM,Florkowski CM,George PM

doi

10.1016/j.jpba.2017.04.055

subject

Has Abstract

pub_date

2017-08-05 00:00:00

pages

125-135

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(16)30873-1

journal_volume

142

pub_type

杂志文章
  • An automated method for the determination of subnanogram concentrations of eprinomectin in bovine plasma.

    abstract::Eprinomectin is a potent anthelmintic compound that kills certain parasitic nematodes and arthropods of cattle. A sensitive and automated bioanalytical assay was developed for quantitation of eprinomectin in bovine plasma in support of clinical development of eprinomectin for use in all classes of cattle. This assay d...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(97)00183-0

    authors: Antonian L,DeMontigny P,Wislocki PG

    更新日期:1998-04-01 00:00:00

  • Enantioselective determination of felodipine in human plasma by chiral normal-phase liquid chromatography and electrospray ionisation mass spectrometry.

    abstract::An analytical method was developed for the determination of the enantiomers of felodipine, a dihydropyridine-type calcium antagonist, in human blood plasma. Felodipine was extracted from plasma using toluene as extraction solvent. The enantiomers were separated on a cellulose tris(4-methyl benzoate) stationary phase (...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(01)00582-9

    authors: Lindmark B,Ahnoff M,Persson BA

    更新日期:2002-01-15 00:00:00

  • Molecular descriptors that influence the amount of drugs transfer into human breast milk.

    abstract::Most drugs are excreted into breast milk to some extent and are bioavailable to the infant. The ability to predict the approximate amount of drug that might be present in milk from the drug structure would be very useful in the clinical setting. The aim of this research was to simplify and upgrade the previously devel...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章,评审

    doi:10.1016/s0731-7085(02)00037-7

    authors: Agatonovic-Kustrin S,Ling LH,Tham SY,Alany RG

    更新日期:2002-06-20 00:00:00

  • Cell-based assays in combination with ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry for screening bioactive capilliposide C metabolites generated by rat intestinal microflora.

    abstract::Many plant-derived glycosides are used as medications. It is common that these glycosides show poor intestinal absorption but their metabolites generated by intestinal microflora demonstrate strong bioactivity. Hence, it is crucial to develop a method for the identification and characterization of the metabolites, and...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2015.11.029

    authors: Cheng Z,Huang M,Chen G,Yang G,Zhou X,Chen C,Zhang Y,Xu Y,Feng Y,Zhang L,Jiang H

    更新日期:2016-02-05 00:00:00

  • Validation of a liquid chromatographic tandem mass spectrometric method for the determination of sumatriptan in human biological fluids.

    abstract::A liquid chromatographic tandem mass spectrometric method for the quantitative determination of sumatriptan base in human plasma and urine has been developed and validated over the concentration range 0.2-20 ng base ml-1. Sumatriptan is a 5-HT1 receptor agonist which has found widespread use in the treatment of migrai...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(97)00220-3

    authors: Cheng KN,Redrup MJ,Barrow A,Williams PN

    更新日期:1998-07-01 00:00:00

  • Benzylpenicillin PVC membrane electrode for the determination of antibiotics in formulations.

    abstract::A PVC (polyvinychloride) ion selective electrode, employing benzyldimethyl-cetylammoniumbenzylpenicillin as sensor, was prepared, characterized and applied to the analysis of commercially available formulations containing benzylpenicillin and other antibiotics of the penicillin or cephalosporin group. The results are ...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/0731-7085(88)80056-6

    authors: Campanella L,Mazzei F,Sbrilli R,Tomassetti M

    更新日期:1988-01-01 00:00:00

  • A simple method for assaying colistimethate sodium in pharmaceutical aerosol samples using high performance liquid chromatography.

    abstract::A rapid and simple reversed-phase high performance liquid chromatography (HPLC) method for the quantitation of colistimethate sodium in pharmaceutical formulations has been developed. The chromatographic separation was performed using a Phenomenex Kinetex XB-C18 column with gradient elution using a mobile phase contai...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2017.04.021

    authors: Metcalf AP,Hardaker LEA,Hatley RHM

    更新日期:2017-08-05 00:00:00

  • Determination of losartan, telmisartan, and valsartan by direct injection of human urine into a column-switching liquid chromatographic system with fluorescence detection.

    abstract::Column-switching high-performance liquid chromatographic (HPLC) method has been developed and validated for quantification of losartan, telmisartan, and valsartan in human urine. Urine samples were diluted on the extraction mobile phase (1:4, v/v) and a volume of 20 microL of this mixture were directly injected onto t...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2009.04.015

    authors: del Rosario Brunetto M,Contreras Y,Clavijo S,Torres D,Delgado Y,Ovalles F,Ayala C,Gallignani M,Estela JM,Martin VC

    更新日期:2009-09-08 00:00:00

  • Liquid chromatographic analysis, stability and protein binding studies of the anti-HIV agent benzoic acid, 2-chloro-5[[(1-methylethoxy)thioxomethyl]amino]-,1-methylethyl ester.

    abstract::A method was developed for the assay of benzoic acid, 2-chloro-5-[[(1-methylethoxyl)thioxomethyl]amino]-,1-meth yle thyl ester (NSC 629243) in hamster, mouse, human and, to a limited extent, dog plasma. Protein in 0.5 ml of plasma was precipitated with four volumes of methanol and the supernatant was analysed for NSC ...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/0731-7085(94)80037-5

    authors: Nomeir AA,McComish MF,Mongan AL,Covey JM,Ferrala NF

    更新日期:1994-05-01 00:00:00

  • Simultaneous determination of triterpenoid saponins in dog plasma by a validated UPLC-MS/MS and its application to a pharmacokinetic study after administration of total saponin of licorice.

    abstract::A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method was developed for simultaneous determination of eight constituents, uralsaponin C, uralsaponin F, 22β-acetoxyl-glycyrrhizin, 24-hydroxy-licorice-saponin E2, licorice-saponin G2, licorice-saponin E2, glycyrrhizin, and licorice...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2012.11.035

    authors: Tao W,Duan J,Guo J,Li J,Tang Y,Liu P,Yang N

    更新日期:2013-03-05 00:00:00

  • Simultaneous determination of amoxycillin and clavulanic acid in pharmaceutical dosage forms by LC with amperometric detection.

    abstract::A simple and sensitive liquid chromatographic method with electrochemical (EC) detection is described for the quantitative determination of amoxycillin and clavulanic acid in pharmaceutical dosage forms. Sample components were separated by a reversed phase C18 column, using a mixture of methanol-phosphate buffer (pH 3...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(00)00507-0

    authors: Aghazadeh A,Kazemifard G

    更新日期:2001-05-01 00:00:00

  • Electron microscopy/energy dispersive X-ray spectroscopy of drug distribution in solid dispersions and interpretation by multifractal geometry.

    abstract::Much contemporary research of poorly water-soluble drugs focuses on amorphous solid dispersions (SDs) for oral drug delivery. Recently, a multifractal formalism has been introduced to describe the distribution of an inorganic carrier in SDs. The present work attempts to directly image model drugs by means of scanning ...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2017.12.020

    authors: Abreu-Villela R,Adler C,Caraballo I,Kuentz M

    更新日期:2018-02-20 00:00:00

  • Development and validation of LC-MS/MS method for the detection and quantification of CpG oligonucleotides 107 (CpG ODN107) and its metabolites in mice plasma.

    abstract::CpG oligodeoxynucleotide 107 (CpG ODN107) could be used as a novel radiosensitizer for glioma. Herein, a novel and sensitive reversed-phase HPLC coupled with electrospray triple quadrupole mass spectrometry (LC-MS/MS) following a one-step C18 solid-phase extraction (SPE) for biological matrix removal was developed and...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2012.06.022

    authors: Cen Y,Li X,Liu D,Pan F,Cai Y,Li B,Peng W,Wu C,Jiang W,Zhou H

    更新日期:2012-11-01 00:00:00

  • An enzyme immunoassay to determine the levels of specific antibodies toward bacterial surface antigens in human immunoglobulin preparations and blood serum.

    abstract::Human polyvalent intravenous immunoglobulin (IVIG) preparations are used as a complementary aid to the proper antimicrobial treatment of severely septic patients in intensive care units (ICUs) and/or as a prophylactic agent to immunocompromised hosts, particularly prone to bacterial infections. There is skepticism abo...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(99)00087-4

    authors: Lamari F,Anastassiou ED,Tsegenidis T,Dimitracopoulos G,Karamanos NK

    更新日期:1999-09-01 00:00:00

  • Identification of a new impurity in lisinopril.

    abstract::LC-UV scan of lisinopril revealed the presence of an unknown impurity (approximately 0.14%) at a relative retention time of 3.26 employing phosphate buffer-acetonitrile as binary gradient system while LC-MS analysis with binary gradient system comprising of a ammonia-ammonium acetate buffer (pH 5.0) and acetonitrile i...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2006.06.046

    authors: Shinde V,Trivedi A,Upadhayay PR,Gupta NL,Kanase DG,Chikate R

    更新日期:2007-01-04 00:00:00

  • Microwave-assisted extraction followed by salting-out phase separation for hierarchical screening of illegal adulterants in aphrodisiac health products by multi-dimensional fingerprint profiling analysis.

    abstract::A novel method for hierarchical screening of illegal adulterants in Fur seal ginseng pills (FSGP) products was developed by microwave-assisted extraction (MAE) coupled to salting-out assisted liquid-liquid extraction (SALLE) with multi-dimensional fingerprint profiling analysis. Using a homogeneous system formed by di...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2020.113774

    authors: Wang K,Jin P,Pi J,Xie X,Zhang Y,Yue Z,Mai X,Fan H,Zhang W

    更新日期:2021-02-05 00:00:00

  • Underlying assumptions in the estimation of secondary structure content in proteins by circular dichroism spectroscopy--a critical review.

    abstract::Recombinant DNA technology has made possible the large-scale production of proteins for pharmaceutical applications. As a result, there has been a renaissance in methodology which can provide information on the structural stability and character of these materials. Circular dichroism (CD) spectroscopy, with its sensit...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章,评审

    doi:10.1016/0731-7085(89)80049-4

    authors: Manning MC

    更新日期:1989-01-01 00:00:00

  • Simultaneous determination of phytoestrogens and key metabolites in breast cancer patients' urine by liquid chromatography-tandem mass spectrometry.

    abstract::A novel, selective and sensitive liquid chromatography-tandem mass spectrometry method has been developed and validated for the simultaneous determination of phytoestrogens and their key metabolites in human urine in this study. This method includes internal standard (IS) screening, analytical sample preparation proce...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2009.06.032

    authors: Yu J,Wu Q,Qiao S,Yu Z,Jin N,Yu B

    更新日期:2009-12-05 00:00:00

  • Forced degradation and impurity profiling: recent trends in analytical perspectives.

    abstract::This review describes an epigrammatic impression of the recent trends in analytical perspectives of degradation and impurities profiling of pharmaceuticals including active pharmaceutical ingredient (API) as well as drug products during 2008-2012. These recent trends in forced degradation and impurity profiling were d...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章,评审

    doi:10.1016/j.jpba.2013.07.013

    authors: Jain D,Basniwal PK

    更新日期:2013-12-01 00:00:00

  • Transport and metabolic profiling studies of amentoflavone in Caco-2 cells by UHPLC-ESI-MS/MS and UHPLC-ESI-Q-TOF-MS/MS.

    abstract::Amentoflavone, a kind of biflavonoid existing in several medicinal plants such as Selaginella moellendorfi and Gingko biloba, possesses anti-inflammatory, antioxidant, anti-virus, anti-tumor activities. In the present study, a new reliable and sensitive UHPLC-ESI-MS/MS method was developed to determine the permeabilit...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2020.113441

    authors: Wang B,Lu Y,Wang R,Liu S,Hu X,Wang H

    更新日期:2020-09-10 00:00:00

  • Optimisation of collection, storage and preparation of rat plasma for 1H NMR spectroscopic analysis in toxicology studies to determine inherent variation in biochemical profiles.

    abstract::Biofluid 1H NMR spectroscopy has been assessed as a tool for toxicological investigations for almost two decades, with most studies focussing on urinary changes. This study has examined variations in the 1H NMR spectroscopy spectra of plasma collected from control rats at different times of the day. The collection, pr...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(02)00455-7

    authors: Deprez S,Sweatman BC,Connor SC,Haselden JN,Waterfield CJ

    更新日期:2002-11-07 00:00:00

  • A sensitive liquid chromatography-mass spectrometry method for simultaneous determination of three diterpenoid esters from Euphorbia lathyris L. in rat plasma.

    abstract::A selective and sensitive liquid chromatography-mass spectrometry (LC-MS) method was developed for the simultaneous determination of Euphorbia factor L(1), Euphorbia factor L(2) and Euphorbia factor L(3) from Euphorbiae semen in rat plasma. Larotaxel was added to a 200 μL plasma sample as the internal standard (IS). T...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2012.09.005

    authors: Meng X,Zhao X,Long Z,Yuan Y,Zhuang H,Bi K,Chen X

    更新日期:2013-01-01 00:00:00

  • Quality evaluation of Angelica acutiloba Kitagawa roots by 1H NMR-based metabolic fingerprinting.

    abstract::The prices of Angelica acutiloba Kitagawa (yamato-toki) and A. acutiloba Kitagawa var. sukiyamae Hikino (hokkai-toki) are now mainly determined according to the sensory quality determined by experts in addition to the physical properties. This method provides a low reliability result for differentiating and qualifying...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2008.04.025

    authors: Tarachiwin L,Katoh A,Ute K,Fukusaki E

    更新日期:2008-09-10 00:00:00

  • Quantitative proton nuclear magnetic resonance for the structural and quantitative analysis of atropine sulfate.

    abstract::This study assessed a general method of quantitative nuclear magnetic resonance (qNMR) for the calibration of atropine sulfate (Active Pharmaceutical Ingredient, API) as reference standard. The spectra were acquired in D2O using maleic acid as the internal standard. Conformational behaviors of tropane ring were observ...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2013.10.036

    authors: Shen S,Yao J,Shi Y

    更新日期:2014-02-01 00:00:00

  • Electrochemical behaviour of tizanidine at solid electrodes.

    abstract::The electrochemical behaviour of tizanidine [5-chloro(delta-2-imidazolinyl-2-amino)-4-benzothiadiazole-2,1,3], a centrally-active skeletal muscle relaxant has been investigated in aqueous media at the carbon paste electrode (CPE). Cyclic voltammetry at different pH values, controlled potential coulometry and comparati...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/0731-7085(91)80077-m

    authors: Kauffmann JM,Lopez Ruiz B,Gotor MF,Patriarche GJ

    更新日期:1992-10-01 00:00:00

  • Analysis of plant extracts by NIRS: simultaneous determination of kavapyrones and water in dry extracts of Piper methysticum Forst.

    abstract::A near-infrared reflection spectroscopy (NIRS) method was developed to determine the total content of kavapyrones, kavain and water in dry extracts of Piper methysticum Forst. (kava kava, Piperaceae). Based on the recorded spectra and the reference data, performed by HPLC and Karl Fischer titration, a chemometrical an...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2004.06.030

    authors: Gaub M,Roeseler Ch,Roos G,Kovar KA

    更新日期:2004-11-19 00:00:00

  • A transcription/translation-based gene signature predicts resistance to chemotherapy in breast cancer.

    abstract::Although chemotherapy is widely used to treat human cancers, most chemotherapeutic agents only benefit a small fraction of patients because of the heterogeneity of cancers. Therefore, identifying of the sensitivity of cancers toward various chemotherapies would be important for choosing of chemotherapeutic regime. In ...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2014.10.018

    authors: He DX,Xia YD,Gu XT,Jin J,Ma X

    更新日期:2015-01-01 00:00:00

  • Free-radical degradation of high-molecular-weight hyaluronan induced by ascorbate plus cupric ions. Testing of bucillamine and its SA981-metabolite as antioxidants.

    abstract::High-molecular-weight hyaluronan (HA) samples were exposed to free-radical chain-degradation reactions induced by ascorbate in the presence of Cu(II) ions - the so-called Weissberger's oxidative system. The concentrations of both reactants [ascorbate, Cu(II)] were comparable to those that may occur during an early sta...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2011.06.015

    authors: Valachová K,Hrabárová E,Priesolová E,Nagy M,Baňasová M,Juránek I,Soltés L

    更新日期:2011-11-01 00:00:00

  • Rapid determination of amoxicillin in premixes by HPLC.

    abstract::A rapid analytical procedure for routine identification and quantification of amoxicillin in premixes by high performance liquid chromatography was developed and tested. The ground premix samples were extracted for 10 min using 100ml extraction mixture water-methanol (800:200, v/v). The extract was analyzed by reverse...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2004.10.010

    authors: Dousa M,Hosmanová R

    更新日期:2005-02-23 00:00:00

  • Application of gas chromatography-tandem mass spectrometry for the determination of amphetamine-type stimulants in blood and urine.

    abstract::Amphetamine, methamphetamine, phentermine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA) are the most popular amphetamine-type stimulants. The use of these substances is a serious societal problem worldwide. In this study, a method based...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2017.09.020

    authors: Woźniak MK,Wiergowski M,Aszyk J,Kubica P,Namieśnik J,Biziuk M

    更新日期:2018-01-30 00:00:00