Sleno Lekha, Volmer Dietrich A
Institute for Marine Biosciences, 1411 Oxford Street, Halifax, Nova Scotia, Canada B3H 3Z1.
Rapid Commun Mass Spectrom. 2006;20(10):1517-24. doi: 10.1002/rcm.2498.
Growing interest in the ability to conduct quantitative assays for small molecules by matrix-assisted laser desorption/ionization (MALDI) has been the driving force for several recent studies. This present work includes the investigation of internal standards for these analyses using a high-repetition rate MALDI triple quadrupole instrument. Certain physicochemical properties are assessed for predicting possible matches for internal standards for different small molecules. The importance of similar molecular weight of an internal standard to its analyte is seen through experiments with a series of acylcarnitines, having a fixed charge site and growing alkyl chain length. Both acetyl- and hexanoyl-carnitine were systematically assessed with several other acylcarnitine compounds as internal standards. The results clearly demonstrate that closely matched molecular weights between analyte and internal standard are essential for acceptable quantitation results. Using alpha-cyano-4-hydroxycinnamic acid as the organic matrix, the similarities between analyte and internal standard remain the most important parameter and not necessarily their even distribution within the solid sample spot. Several 4-quinolone antibiotics as well as a diverse group of pharmaceutical drugs were tested as internal standards for the 4-quinolone, ciprofloxacin. Quantitative results were shown using the solution-phase properties, log D and pKa, of these molecules. Their distribution coefficients, log D, are demonstrated as a fundamental parameter for similar crystallization patterns of analyte and internal standard. In the end, it was also possible to quantify ciprofloxacin using a drug from a different compound class, namely quinidine, having a similar log D value as the analyte.
对通过基质辅助激光解吸/电离（MALDI）对小分子进行定量分析能力的兴趣日益浓厚，这是近期多项研究的驱动力。本工作包括使用高重复率MALDI三重四极杆仪器研究这些分析的内标。评估某些物理化学性质以预测不同小分子内标的可能匹配情况。通过对一系列具有固定电荷位点和不断增长的烷基链长度的酰基肉碱进行实验，可见内标与分析物分子量相似的重要性。以乙酰肉碱和己酰肉碱为研究对象，系统地评估了其他几种酰基肉碱化合物作为内标。结果清楚地表明，分析物与内标之间紧密匹配的分子量对于获得可接受的定量结果至关重要。使用α-氰基-4-羟基肉桂酸作为有机基质时，分析物与内标的相似性仍然是最重要的参数，而不一定是它们在固体样品点内的均匀分布。测试了几种4-喹诺酮类抗生素以及一组不同的药物作为4-喹诺酮类药物环丙沙星的内标。利用这些分子的溶液相性质log D和pKa展示了定量结果。它们的分配系数log D被证明是分析物和内标具有相似结晶模式的一个基本参数。最后，还能够使用来自不同化合物类别的药物奎尼丁对环丙沙星进行定量，奎尼丁的log D值与分析物相似。
