Rapid screening of high-risk patients for disorders of purine and pyrimidine metabolism using HPLC-electrospray tandem mass spectrometry of liquid urine or urine-soaked filter paper strips

Tetsuya Ito, André B.P. Van Kuilenburg, Albert H. Bootsma, Anja J. Haasnoot, Arno Van Cruchten, Yoshiro Wada, Albert H. Van Gennip

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Background: A rapid and specific screening method for patients at risk of inherited disorders of purine and pyrimidine metabolism is desirable because symptoms are varied and nonspecific. The aim of this study was to develop a rapid and specific method for screening with use of liquid urine samples or urine-soaked filter paper strips. Methods: Reverse-phase HPLC was combined with electrospray ionization (ESI), tandem mass spectrometry (MS/MS), and detection performed by multiple reaction monitoring. Transitions and instrument settings were established for 17 purines or pyrimidines. Stable-isotope-labeled reference compounds were used as internal standards when available. Results: Total analysis time of this method was 15 min, approximately one-third that of conventional HPLC with ultraviolet detection. Recoveries were 96-107% in urine with added analyte, with two exceptions (hypoxanthine, 64%; xanthine, 79%), and 89-110% in urine-soaked filter paper strips, with three exceptions (hypoxanthine, 65%; xanthine, 77%; 5- hydroxymethyluracil, 80%). The expected abnormalities were easily found in samples from patients with purine nucleoside phosphorylase deficiency, ornithine transcarbamylase deficiency, molybdenum cofactor deficiency, adenylosuccinase deficiency, or dihydropyrimidine dehydrogenase deficiency. Conclusions: HPLC-ESI MS/MS of urine allows rapid screening for disorders of purine and pyrimidine metabolism. The filter paper strips offer the advantage of easy collection, transport, and storage of the urine samples. (C) 2000 American Association for Clinical Chemistry.

Original languageEnglish
Pages (from-to)445-452
Number of pages8
JournalClinical Chemistry
Volume46
Issue number4
Publication statusPublished - 28-04-2000

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Tandem Mass Spectrometry
Metabolism
Mass spectrometry
Electrospray ionization
Screening
Hypoxanthine
Xanthine
High Pressure Liquid Chromatography
Urine
Adenylosuccinate Lyase
Liquids
Dihydrouracil Dehydrogenase (NADP)
Ornithine Carbamoyltransferase
Purine-Nucleoside Phosphorylase
Pyrimidines
Purines
Isotopes
Dihydropyrimidine Dehydrogenase Deficiency
Ornithine Carbamoyltransferase Deficiency Disease
Recovery

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Ito, Tetsuya ; Van Kuilenburg, André B.P. ; Bootsma, Albert H. ; Haasnoot, Anja J. ; Van Cruchten, Arno ; Wada, Yoshiro ; Van Gennip, Albert H. / Rapid screening of high-risk patients for disorders of purine and pyrimidine metabolism using HPLC-electrospray tandem mass spectrometry of liquid urine or urine-soaked filter paper strips. In: Clinical Chemistry. 2000 ; Vol. 46, No. 4. pp. 445-452.
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abstract = "Background: A rapid and specific screening method for patients at risk of inherited disorders of purine and pyrimidine metabolism is desirable because symptoms are varied and nonspecific. The aim of this study was to develop a rapid and specific method for screening with use of liquid urine samples or urine-soaked filter paper strips. Methods: Reverse-phase HPLC was combined with electrospray ionization (ESI), tandem mass spectrometry (MS/MS), and detection performed by multiple reaction monitoring. Transitions and instrument settings were established for 17 purines or pyrimidines. Stable-isotope-labeled reference compounds were used as internal standards when available. Results: Total analysis time of this method was 15 min, approximately one-third that of conventional HPLC with ultraviolet detection. Recoveries were 96-107{\%} in urine with added analyte, with two exceptions (hypoxanthine, 64{\%}; xanthine, 79{\%}), and 89-110{\%} in urine-soaked filter paper strips, with three exceptions (hypoxanthine, 65{\%}; xanthine, 77{\%}; 5- hydroxymethyluracil, 80{\%}). The expected abnormalities were easily found in samples from patients with purine nucleoside phosphorylase deficiency, ornithine transcarbamylase deficiency, molybdenum cofactor deficiency, adenylosuccinase deficiency, or dihydropyrimidine dehydrogenase deficiency. Conclusions: HPLC-ESI MS/MS of urine allows rapid screening for disorders of purine and pyrimidine metabolism. The filter paper strips offer the advantage of easy collection, transport, and storage of the urine samples. (C) 2000 American Association for Clinical Chemistry.",
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Rapid screening of high-risk patients for disorders of purine and pyrimidine metabolism using HPLC-electrospray tandem mass spectrometry of liquid urine or urine-soaked filter paper strips. / Ito, Tetsuya; Van Kuilenburg, André B.P.; Bootsma, Albert H.; Haasnoot, Anja J.; Van Cruchten, Arno; Wada, Yoshiro; Van Gennip, Albert H.

In: Clinical Chemistry, Vol. 46, No. 4, 28.04.2000, p. 445-452.

Research output: Contribution to journalArticle

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T1 - Rapid screening of high-risk patients for disorders of purine and pyrimidine metabolism using HPLC-electrospray tandem mass spectrometry of liquid urine or urine-soaked filter paper strips

AU - Ito, Tetsuya

AU - Van Kuilenburg, André B.P.

AU - Bootsma, Albert H.

AU - Haasnoot, Anja J.

AU - Van Cruchten, Arno

AU - Wada, Yoshiro

AU - Van Gennip, Albert H.

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Y1 - 2000/4/28

N2 - Background: A rapid and specific screening method for patients at risk of inherited disorders of purine and pyrimidine metabolism is desirable because symptoms are varied and nonspecific. The aim of this study was to develop a rapid and specific method for screening with use of liquid urine samples or urine-soaked filter paper strips. Methods: Reverse-phase HPLC was combined with electrospray ionization (ESI), tandem mass spectrometry (MS/MS), and detection performed by multiple reaction monitoring. Transitions and instrument settings were established for 17 purines or pyrimidines. Stable-isotope-labeled reference compounds were used as internal standards when available. Results: Total analysis time of this method was 15 min, approximately one-third that of conventional HPLC with ultraviolet detection. Recoveries were 96-107% in urine with added analyte, with two exceptions (hypoxanthine, 64%; xanthine, 79%), and 89-110% in urine-soaked filter paper strips, with three exceptions (hypoxanthine, 65%; xanthine, 77%; 5- hydroxymethyluracil, 80%). The expected abnormalities were easily found in samples from patients with purine nucleoside phosphorylase deficiency, ornithine transcarbamylase deficiency, molybdenum cofactor deficiency, adenylosuccinase deficiency, or dihydropyrimidine dehydrogenase deficiency. Conclusions: HPLC-ESI MS/MS of urine allows rapid screening for disorders of purine and pyrimidine metabolism. The filter paper strips offer the advantage of easy collection, transport, and storage of the urine samples. (C) 2000 American Association for Clinical Chemistry.

AB - Background: A rapid and specific screening method for patients at risk of inherited disorders of purine and pyrimidine metabolism is desirable because symptoms are varied and nonspecific. The aim of this study was to develop a rapid and specific method for screening with use of liquid urine samples or urine-soaked filter paper strips. Methods: Reverse-phase HPLC was combined with electrospray ionization (ESI), tandem mass spectrometry (MS/MS), and detection performed by multiple reaction monitoring. Transitions and instrument settings were established for 17 purines or pyrimidines. Stable-isotope-labeled reference compounds were used as internal standards when available. Results: Total analysis time of this method was 15 min, approximately one-third that of conventional HPLC with ultraviolet detection. Recoveries were 96-107% in urine with added analyte, with two exceptions (hypoxanthine, 64%; xanthine, 79%), and 89-110% in urine-soaked filter paper strips, with three exceptions (hypoxanthine, 65%; xanthine, 77%; 5- hydroxymethyluracil, 80%). The expected abnormalities were easily found in samples from patients with purine nucleoside phosphorylase deficiency, ornithine transcarbamylase deficiency, molybdenum cofactor deficiency, adenylosuccinase deficiency, or dihydropyrimidine dehydrogenase deficiency. Conclusions: HPLC-ESI MS/MS of urine allows rapid screening for disorders of purine and pyrimidine metabolism. The filter paper strips offer the advantage of easy collection, transport, and storage of the urine samples. (C) 2000 American Association for Clinical Chemistry.

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