Liquid chromatography and mass spectrometry of haem biosynthetic intermediates: a review

Benton, Christopher M.; Lim, Chang Kee

doi:10.1002/bmc.2772

Cited by 9 publications

(8 citation statements)

References 159 publications

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“…Although ALA and PBG can be monitored in both positive and negative ionization modes (Benton and Lim, ; Benton et al ., ), positive ionization mode was used for this study as it offered increased sensitivity. The protonated [M + H] + PBG ion ( m/z 227) showed significant loss of NH 3 in the ion source ([M + H − NH 3 ] + ) to give a stable, positively charged methylenepyrrolenine ion ( m/z 210; Lord et al ., ; Benton et al ., 2012a, 2012b), as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Direct and simultaneous quantitation of 5‐aminolaevulinic acid and porphobilinogen in human serum or plasma by hydrophilic interaction liquid chromatography–atmospheric pressure chemical ionization/tandem mass spectrometry

Benton

Couchman

Marsden

et al. 2012

Biomedical Chromatography

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Serum/plasma concentrations of 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG) are elevated in patients with acute hepatic porphyrias, especially during acute attacks. Current assays require lengthy sample pre-treatment and derivatization steps. We report here a rapid, sensitive and specific hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the direct and simultaneous quantitation of ALA and PBG in serum or plasma following simple protein precipitation with acetonitrile and centrifugation prior to injection. ALA and PBG were detected using selected reaction monitoring mode, following positive atmospheric pressure chemical ionization. Calibration was linear from 0.05 to 50 µmol/L for ALA and PBG. For both analytes, imprecision (relative standard deviation) was <13% and accuracy (percentage nominal concentrations) was between 92 and 107%. The method was successfully applied to the measurement of ALA and PBG in serum or plasma samples for the screening, biochemical diagnosis and treatment monitoring of patients with acute hepatic porphyrias.

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Section: Resultsmentioning

confidence: 99%

Direct and simultaneous quantitation of 5‐aminolaevulinic acid and porphobilinogen in human serum or plasma by hydrophilic interaction liquid chromatography–atmospheric pressure chemical ionization/tandem mass spectrometry

Benton

Couchman

Marsden

et al. 2012

Biomedical Chromatography

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“…Eluent A was 10% acetonitrile (v/v) in 1 mol/l aqueous ammonium acetate – acetic acid buffer, pH 5.16 and eluent B was 10% acetonitrile in methanol. Previous studies have shown that a high molar concentration of ammonium acetate buffer (1 mol/l, pH 5.16) is essential for the separation of type I and III uroporphyrin and heptacarboxylic acid porphyrin isomers. Lower molar concentrations tend to give peak broadening with the consequent loss of chromatographic resolution.…”

Section: Methodsmentioning

confidence: 99%

“…We have developed LC‐MS and LC‐MS/MS systems for the rapid separation and characterisation of porphyrins in biological materials . Here we report the further separation and characterisation of hydroxyisocoproporphyrin, ketoisocoproporphyrin, deethylisocoproporphyrin and isocoproporphyrin using UHPLC‐ESI‐exact mass MS/MS, which will greatly assist in the structural elucidation of isocoproporphyrin and its derivatives.…”

Section: Introductionmentioning

confidence: 99%

Separation and fragmentation study of isocoproporphyrin derivatives by UHPLC-ESI-exact mass MS/MS and identification of a new isocoproporphyrin sulfonic acid metabolite

et al. 2014

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Isocoproporphyrin and its derivatives are commonly used as biomarkers of porphyria cutanea tarda, heavy metal toxicity and hexachlorobenzene (HCB) intoxication in humans and animals. However, most are isobaric with other porphyrins and reference materials are unavailable commercially. The structural characterisation of these porphyrins is important but very little data is available. We report here the separation and characterisation of isocoproporphyrin, deethylisocoproporphyrin, hydroxyisocoproporphyrin and ketoisocoproporphyrin, isolated in the faeces of rats fed with a diet containing HCB, by ultra high performance liquid chromatography-exact mass tandem mass spectrometry (UHPLC-MS/MS). Furthermore, we report the identification and characterisation of a previously unreported porphyrin metabolite, isocoproporphyrin sulfonic acid isolated in the rat faeces. The measured mass-to-charge ratio (m/z) of the precursor ion was m/z 735.2338, corresponding to a molecular formula of C36H39N4O11S with an error of 0.3 ppm from the calculated m/z 735.2336. The MS/MS data was consistent with an isocoproporphyrin sulfonic acid structure, derived from dehydroisocoproporphyrinogen by sulfonation of the vinyl group. The metabolite was present in a greater abundance than other isocoproporphyrin derivatives and may be a more useful biomarker for HCB intoxication.

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“…While ALA and PBG, the early precursors of heme synthesis pathway, increase during the acute episodes, the increase in porphyrins, i.e. the late substrates, becomes more significant in the chronic period [3].…”

Section: Introductionmentioning

confidence: 99%

A Simple Method for Quantification of Five Urinary Porphyrins, Porphobilinogen and 5-Aminolevulinic Acid, Using Liquid Chromatography Tandem Mass Spectrometry

Doğan

Serdar

Murat³

et al. 2017

Ind J Clin Biochem

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Analysis of porphyrins and 5-aminolevulinic acid (ALA), porphobilinogen (PBG) in physiological liquids is required for diagnosis and follow-up of porphyrias. High performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS) methods with higher specificity and sensitivity have been developed. The major disadvantage of those methods is that they require longer extraction times due to their matrix effects. The present study suggests a simple, fast, sensitive, and specific assay for determination of Coproporphyrin, 5-carboxylporphyrin, 6-carboxylporphyrin, 7-carboxylporphyrin, Uroporphyrin I and ALA, PBG in urine sample by direct injection without sample pre-treatment using LC-MS. For the purposes of the present study LC-MS device was set to multiple reaction monitoring (MRM) and positive ion mode. Porphyrins and ALA, porphobilinogen were characterized by their MS/MS product ion, spectra. ALA, PBG and 5 porphyrins were detected simultaneously. Limit of detection for Coproporphyrin, 5-carboxylporphyrin, 6-carboxylporphyrin, 7-carboxylporphyrin, Uroporphyrin I were 2 nmol/L, where it was 5 lmol/L for ALA and 2 lmol/L for porphobilinogen. The present study suggests that the present method is very effective compared to many other available methods for it does not require pre-treatment, provides simultaneous results of ALA, PBG and 5 porphyrins quantitatively in a shorter span of time, and has suitable sensitivity and selectivity. LC-MS technique was used clinically for the determination of urine porphyrin levels.

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Liquid chromatography and mass spectrometry of haem biosynthetic intermediates: a review

Cited by 9 publications

References 159 publications

Direct and simultaneous quantitation of 5‐aminolaevulinic acid and porphobilinogen in human serum or plasma by hydrophilic interaction liquid chromatography–atmospheric pressure chemical ionization/tandem mass spectrometry

Direct and simultaneous quantitation of 5‐aminolaevulinic acid and porphobilinogen in human serum or plasma by hydrophilic interaction liquid chromatography–atmospheric pressure chemical ionization/tandem mass spectrometry

Separation and fragmentation study of isocoproporphyrin derivatives by UHPLC-ESI-exact mass MS/MS and identification of a new isocoproporphyrin sulfonic acid metabolite

A Simple Method for Quantification of Five Urinary Porphyrins, Porphobilinogen and 5-Aminolevulinic Acid, Using Liquid Chromatography Tandem Mass Spectrometry

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