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Simultaneous quantitation of serum caffeine and its metabolites by ultra‐high‐performance liquid chromatography–tandem mass spectrometry for CYP1A2 activity prediction in premature infants
Author(s) -
Jiang Zhouhong,
Gao Xiangbo,
Liang Jianfeng,
Ni Shaoqing
Publication year - 2021
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.5141
Subject(s) - chemistry , cyp1a2 , paraxanthine , chromatography , formic acid , caffeine , mass spectrometry , theobromine , tandem mass spectrometry , liquid chromatography–mass spectrometry , selected reaction monitoring , theophylline , metabolism , biochemistry , cytochrome p450 , pharmacology , endocrinology , medicine
Caffeine (CA) is accepted as a probe of cytochrome P450 1A2 enzyme (CYP1A2) activity and is commonly used in premature infants with great inter‐individual variability of metabolism. To evaluate the change characteristics of CYP1A2 activity in premature infants, an ultra‐high‐performance liquid chromatography–tandem mass spectrometry method was developed and optimized for the simultaneous quantitation of serum CA and its major metabolites, including paraxanthine (PX), theophylline (TP) and theobromine (TB), in premature infants. A C 18 column and gradient elution with 0.1% formic acid in methanol and 0.1% formic acid in water at a flow rate of 0.3 mL/min were used for compound separation. The mass spectrometer monitored the transitions of CA ( m/z 195.0 → 138.0), CA‐d9 ( m/z 204.0 → 144.1), PX ( m/z 181.0 → 124.1), TP ( m/z 181.0 → 123.9) and TB ( m/z 181.0 → 138.0) using multiple reaction monitoring in positive ion mode. CYP1A2 activity was evaluated by serum molar concentration ratios of CA and its metabolites. The results showed that CYP1A2 has a significant positive correlation with the clearance of CA, and was affected by current weight and CYP1A2*1C. The results suggested that the serum concentration ratios of CA metabolites could be used to predict the changes in CYP1A2 enzyme activity in premature infants.