Development and clinical application of high performance liquid chromatography for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine

Junko Kizu, Shigekazu Watanabe, Nobuhiro Yasuno, Yoshihiro Arakawa, Sonoko Uzu, Susumu Kanda, Fusako Komoda, Tsutomu Iwata, Hiroshi Hayakawa, Tetsuo Hayakawa, Kazuhiro Imai

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine or caffeine metabolites. The method is simple and of practical use because it is applicable even to plasma samples from patients who take caffeine-containing beverages. The method was also reproducible with a coefficient of variation of less than 5% for each analyte. The levels of theophylline, determined by HPLC, were validated by their high correlation to the levels obtained by fluorescence polarization immunoassay. HPLC was used to determine theophylline levels in patients with bronchial asthma. The data revealed that the ratio of 1,3-dimethyluric acid, the major metabolite of theophylline, to theophylline concentration in the plasma was within a narrow range in most patients (0.055 ± 0.01, n = 66), regardless of the method of theophylline administration or the time of blood sampling. Conversely, this ratio was as low as 0.027 ± 0.005 in the patient with a long plasma half-life of theophylline. These results suggest that it may be possible to predict the plasma half-life of theophylline for each patient from a single blood sample. This may be useful when planning theophylline administration, especially in patients with abnormal theophylline metabolism.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalBiomedical Chromatography
Volume13
Issue number1
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

High performance liquid chromatography
Theophylline
Metabolites
Caffeine
High Pressure Liquid Chromatography
Plasmas
Half-Life
Blood
Fluorescence Polarization Immunoassay
Beverages
Metabolism
Asthma
Fluorescence
Polarization
Sampling
Planning

ASJC Scopus subject areas

  • Analytical Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Development and clinical application of high performance liquid chromatography for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine. / Kizu, Junko; Watanabe, Shigekazu; Yasuno, Nobuhiro; Arakawa, Yoshihiro; Uzu, Sonoko; Kanda, Susumu; Komoda, Fusako; Iwata, Tsutomu; Hayakawa, Hiroshi; Hayakawa, Tetsuo; Imai, Kazuhiro.

In: Biomedical Chromatography, Vol. 13, No. 1, 1999, p. 15-23.

Research output: Contribution to journalArticle

Kizu, Junko ; Watanabe, Shigekazu ; Yasuno, Nobuhiro ; Arakawa, Yoshihiro ; Uzu, Sonoko ; Kanda, Susumu ; Komoda, Fusako ; Iwata, Tsutomu ; Hayakawa, Hiroshi ; Hayakawa, Tetsuo ; Imai, Kazuhiro. / Development and clinical application of high performance liquid chromatography for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine. In: Biomedical Chromatography. 1999 ; Vol. 13, No. 1. pp. 15-23.
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