Triolo A, Agostini O, Bonelli F
A. Menarini SRL, Analytical Research Department, Florence, Italy.
Biol Mass Spectrom. 1994 Feb;23(2):91-6. doi: 10.1002/bms.1200230208.
Analysis of urinary metabolites of isbufylline (1,3-dimethyl-7-(2-methylpropyl)xanthine) in healthy male volunteers after oral administration of a single dose of 320 mg was undertaken by high-performance liquid chromatography/mass spectrometry (HPLC/MS with thermospray ionization. Filtered urines were directed injected into the HPLC/MS system, equipped with a Lichrospher 100 RP 18 analytical column. The mobile phase was 0.1 M, pH 3.7 ammonium acetate in water and acetonitrile; the composition was varied linearly from 5% to 40% of the organic modifier in 40 min with a flow rate of 1 ml min-1. Three more chromatographic peaks appeared in urines from treated subjects as compared to untreated ones; their probable quasi-molecular ions were at m/z 253, 239 and 267 respectively, while the original drug, of 236 Da, was not present in appreciable quantity. The collisionally activated daughter ion spectra of the above ions allowed identification of 1,3-dimethyl-7-(3-hydroxy-2-methylpropyl)xanthine (D3OHMPX), 1-methyl-7-(2-hydroxy-2-methylpropyl)xanthine (M2OHMPX), and 1,3-dimethyl-(2-carboxypropyl)xanthine (D2CMPX), the first one being present as glucuronic acid conjugate.
采用高效液相色谱/质谱联用技术（带热喷雾电离的HPLC/MS）对健康男性志愿者单次口服320 mg异布茶碱（1,3 - 二甲基 - 7 -（2 - 甲基丙基）黄嘌呤）后的尿液代谢产物进行分析。将过滤后的尿液直接注入配备Lichrospher 100 RP 18分析柱的HPLC/MS系统。流动相为0.1 M、pH 3.7的醋酸铵水溶液和乙腈；有机改性剂的组成在40分钟内从5%线性变化至40%，流速为1 ml/min。与未处理受试者的尿液相比，处理后受试者的尿液中出现了另外三个色谱峰；它们可能的准分子离子分别为m/z 253、239和267，而原药物分子量为236 Da，含量并不显著。上述离子的碰撞激活子离子光谱有助于鉴定1,3 - 二甲基 - 7 -（3 - 羟基 - 2 - 甲基丙基）黄嘌呤（D3OHMPX）、1 - 甲基 - 7 -（2 - 羟基 - 2 - 甲基丙基）黄嘌呤（M2OHMPX）和1,3 - 二甲基 -（2 - 羧基丙基）黄嘌呤（D2CMPX），其中第一个以葡萄糖醛酸结合物形式存在。
