Boehringer Ingelheim Ltd, Ellesfield Avenue, Bracknell, Berkshire RG12 8YS, UK.
J Pharm Biomed Anal. 2010 Jun 5;52(2):210-5. doi: 10.1016/j.jpba.2010.01.003. Epub 2010 Jan 11.
The degradation pathways of salbutamol in ethanolic solutions have been investigated and three potential ethyl ether degradation products have been identified. Two have been confirmed as salbutamol ethyl ethers and the third as a diethyl ether. All three degradation products have been structurally elucidated by LC-MS-MS (TOF and tandem quadrupole). The two ethyl ethers have a molecular weight of 267 Da (28 units higher than salbutamol) and are structural isomers (molecules with the same molecular weight but different structural arrangements). The molecular weight of the two ethyl ethers is consistent with the addition of one ethyl group to the salbutamol molecule and elimination of one water molecule. The molecular weight of the diethyl ether is 295 Da (56 units higher than salbutamol) and is consistent with the addition of two ethyl groups to the salbutamol molecule and elimination of two water molecules. A plausible degradation mechanism for the formation of the salbutamol ethyl ethers is the acid-catalysed dehydration of alcohols. Acidic pH is required to drive the degradation of salbutamol in ethanolic solution. Higher degradation levels of salbutamol ethyl ethers are achieved in acidic pH solutions. Levels of the two salbutamol ethyl ethers reach a maximum at an ethanol concentration of around 20%. Levels of the diethyl ether increase linearly with ethanol concentration, until it becomes the major degradation product in high concentration ethanolic solutions (>or=30%).
已研究了沙丁胺醇在乙醇溶液中的降解途径，并鉴定出了三种潜在的乙基醚降解产物。其中两种已确认为沙丁胺醇乙基醚，第三种为二乙醚。所有三种降解产物均通过 LC-MS-MS（TOF 和串联四极杆）进行了结构阐明。两种乙基醚的分子量为 267 Da（比沙丁胺醇高 28 个单位），并且是结构异构体（分子量相同但结构排列不同的分子）。两种乙基醚的分子量与沙丁胺醇分子上添加一个乙基基团和消除一个水分子一致。二乙醚的分子量为 295 Da（比沙丁胺醇高 56 个单位），与沙丁胺醇分子上添加两个乙基基团和消除两个水分子一致。形成沙丁胺醇乙基醚的合理降解机制是醇的酸催化脱水。酸性 pH 值是驱动沙丁胺醇在乙醇溶液中降解所必需的。在酸性 pH 值溶液中，沙丁胺醇乙基醚的降解水平更高。两种沙丁胺醇乙基醚的水平在乙醇浓度约为 20%时达到最大值。二乙醚的水平随乙醇浓度呈线性增加，直到在高浓度乙醇溶液（>或=30%）中成为主要降解产物。
