Lampinen Salomonsson Matilda, Bondesson Ulf, Hedeland Mikael
Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, SE-751 23 Uppsala, Sweden.
J Mass Spectrom. 2009 May;44(5):742-54. doi: 10.1002/jms.1551.
Derivatization with 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC) has been successfully used as a tool to differentiate between aromatic and aliphatic O-glucuronides of hydroxypropranolol. The analyses were performed with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) with both a triple quadrupole and an ion trap instrument. Hydroxylated forms of propranolol can be glucuronidated in aliphatic as well as aromatic positions. These isoforms are not distinguishable by tandem MS alone, as they both initially lose 176 Da, i.e. monodehydrated glucuronic acid, giving back the aglycone. Two in vitro systems were set up for the production of propranolol metabolites. The obtained isomers of 4'-hydroxypropranolol glucuronide were determined to correspond to one aliphatic and one aromatic form, using chemical derivatization with DMISC and LC-MS(n). DMISC was shown to react with the secondary amine in the case where the naphtol was occupied by the glucuronyl moiety, resulting in a different fragmentation pattern compared with that of the aliphatic glucuronide, where the naphtol group was accessible to derivatization.
用1,2 - 二甲基咪唑 - 4 - 磺酰氯（DMISC）进行衍生化已成功用作区分羟基普萘洛尔芳香族和脂肪族O - 葡萄糖醛酸苷的工具。分析采用液相色谱 - 电喷雾电离 - 串联质谱（LC - ESI - MS/MS），使用三重四极杆和离子阱仪器进行。普萘洛尔的羟基化形式可在脂肪族和芳香族位置进行葡萄糖醛酸化。这些异构体仅通过串联质谱无法区分，因为它们最初都会失去176 Da，即单脱水葡萄糖醛酸，从而得到苷元。建立了两个体外系统用于生产普萘洛尔代谢物。使用DMISC化学衍生化和LC - MS(n)，确定所获得的4'-羟基普萘洛尔葡萄糖醛酸苷的异构体对应于一种脂肪族形式和一种芳香族形式。结果表明，在萘酚被葡萄糖醛酰基部分占据的情况下，DMISC会与仲胺发生反应，与脂肪族葡萄糖醛酸苷相比，产生不同的碎片模式，脂肪族葡萄糖醛酸苷的萘酚基团可进行衍生化。
