A sensitive liquid chromatography-tandem mass spectrometry (LC-MS) method was developed for the screening of five β-blockers (BBs), including atenolol, metoprolol, bisoprolol, propranolol, and betaxolol, in rabbit plasma. An inhouse prepared hydrazonoyl chloride compound (UOSA54) and dansyl chloride (DNS) were successfully coupled with BBs via the amino functional group and analyzed by LC-MS/MS. The excess hydrazonoyl chloride was characterized by a negligible ionization suppression at the electrospray-ionization (ESI) source, which enables the analysis of BBs at a low concentration level. The relative ESI-MS response of derivatized to underivatized BBs was enhanced 2.3 to 3.7-fold. The developed method could be applied for screening of BBs in samples by searching the most abundant MS product ions, including m/z 169 and 211, in addition to the precursor ion and the cleavage of ether moiety. The method could be applied for trace analysis and screening of BBs abuse. The use of UOSA54 was adventitious over dansylated derivatives because of minimal reaction by-products and the negligible ionization suppression effect. The extraction efficiency of BBs from rabbit plasma was improved to reach 77.5–93.9% using tert-butylamine and Chromabond® C18ec-100 mg column. The optimal reaction conditions were optimized and validated. The linear range of analyzed BBs in rabbit plasma was within the range of 0.1 to 25.0 ng/mL, while the limit of quantification (LO Q) was ranged from 0.10 to 0.25 ng/mL.

开发了一种灵敏的液相色谱-串联质谱（LC-MS）方法，用于在兔血浆中筛选5种β-受体阻滞剂（BBs），包括阿替洛尔，美托洛尔，比索洛尔，普萘洛尔和倍他洛尔。内部制备的酰氯化合物（UOSA54）和丹酰氯（DNS）已通过氨基官能团与BBs成功偶联，并通过LC-MS / MS分析。过量的酰肼基氯的特点是在电喷雾电离（ESI）源处的电离抑制作用可忽略不计，这使得在低浓度下分析BBs成为可能。衍生化为未衍生化的BB的相对ESI-MS反应提高了2.3到3.7倍。通过搜索最丰富的MS产物离子（包括m/ z 169和211，除了前体离子和醚部分的裂解。该方法可用于痕量分析和对BBs滥用的筛选。UOSA54相对于丹磺酰化衍生物是不方便使用的，因为其反应副产物最少且电离抑制作用可忽略不计。使用叔丁胺和Chromabond®C18ec-100 mg色谱柱可提高兔血浆中BB的提取效率，达到77.5–93.9％。优化并验证了最佳反应条件。兔血浆中分析的BBs的线性范围在0.1至25.0 ng / mL的范围内，而定量限（LO Q）在0.10至0.25 ng / mL的范围内。