Department of Pharmacy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Biostatistics Unit, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Biomed Chromatogr. 2021 Sep;35(9):e5141. doi: 10.1002/bmc.5141. Epub 2021 Jun 28.
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 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.
咖啡因（CA）被认为是细胞色素 P450 1A2 酶（CYP1A2）活性的探针，并且在代谢个体间差异极大的早产儿中常被使用。为了评估早产儿 CYP1A2 活性的变化特征，开发并优化了一种超高效液相色谱-串联质谱法，用于同时定量分析早产儿血清 CA 及其主要代谢物，包括可可碱（PX）、茶碱（TP）和可可因（TB）。使用 C 柱和甲醇中 0.1%甲酸和水中 0.1%甲酸的梯度洗脱，流速为 0.3mL/min 进行化合物分离。质谱仪以正离子模式监测 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）和 TB（m/z 181.0→138.0）的跃迁。CYP1A2 活性通过 CA 和其代谢物的血清摩尔浓度比来评估。结果表明，CYP1A2 与 CA 的清除率呈显著正相关，并受当前体重和 CYP1A2*1C 的影响。结果表明，CA 代谢物的血清浓度比可用于预测早产儿 CYP1A2 酶活性的变化。
