Lindberg C, Paulson J, Edsbäcker S
Pharmacokinetics Laboratory, AB Draco, Lund, Sweden.
Biomed Environ Mass Spectrom. 1987 Oct;14(10):535-41. doi: 10.1002/bms.1200141002.
A moving belt interface was used to identify budesonide metabolites, obtained from rat and mouse liver incubations, by liquid chromatography/mass spectrometry (LC/MS). The metabolites were separated on a small-bore C18 column with an ethanol/water gradient as mobile phase at a flow rate of 0.2 ml min-1. A spray device was used for deposition of the aqueous solvent on to the belt. Chemical ionization mass spectra were obtained with methane as the reagent gas. Deuterium-labelled budesonide, which was used to facilitate metabolite identification by the isotope cluster technique, was found to be slightly separated from the unlabelled analogue on the LC column. Incubations were also performed under 18O2 to elucidate the mechanism of a new metabolic pathway (16 alpha, 17 alpha-acetal splitting) and to confirm the oxidative nature of reactions leading to hydroxylated metabolites. The moving belt LC/MS technique afforded higher sensitivity, and gave more abundant MH+ ions of the compounds studied, than previously found by direct probe mass spectrometry. Phthalate ester background, partly from the polymide belt, complicated the identification of minor metabolites.
采用移动带接口，通过液相色谱/质谱联用（LC/MS）技术对从大鼠和小鼠肝脏孵育物中获得的布地奈德代谢产物进行鉴定。代谢产物在小内径C18柱上分离，以乙醇/水梯度作为流动相，流速为0.2 ml/min。使用喷雾装置将水性溶剂沉积到带上。以甲烷作为反应气获得化学电离质谱。发现用于通过同位素簇技术促进代谢产物鉴定的氘代布地奈德在LC柱上与未标记的类似物稍有分离。还在18O2条件下进行孵育，以阐明新代谢途径（16α，17α - 缩醛裂解）的机制，并确认导致羟基化代谢产物的反应的氧化性质。与先前通过直接探针质谱法发现的相比，移动带LC/MS技术具有更高的灵敏度，并且所研究化合物的MH+离子更丰富。部分来自聚酰亚胺带的邻苯二甲酸酯背景使微量代谢产物的鉴定变得复杂。
