In this study a heart-cutting 2D-LC method was successfully developed and optimized in order to discriminate and quantitate (S)-propranolol, (R)-propranolol, and its hydroxy metabolites, namely the isomeric (S)-4'‑hydroxy propranolol, (R)-4'‑hydroxy propranolol, (S)-5'‑hydroxy propranolol, (R)-5'‑hydroxy propranolol, (S)-7'-hydroxy propranolol, and (R)-7'‑hydroxy propranolol in one chromatographic run. Thereby, experiments investigating chiral discrimination in ring hydroxylation of propranolol were made feasible. Analysis of human urine samples after administration of a single oral dose of 40 mg of propranolol clearly revealed considerable chiral shifts in propranolol and its 4'-, 5'-, and 7'-hydroxy metabolites. Furthermore, the excretion rates of the individual (S)- and (R)-enantiomers were continuously monitored over 24 h post administration. Studies were performed utilizing a 2D-LC system hyphenated to a triple quadrupole mass spectrometer. The chromatographic system was endued with a reversed phase column (phenyl-hexyl) in first dimension and a teicoplanin based chiral column in second dimension. The method was basically validated and successfully evaluated as robust. Calibration was performed achieving accuracy between 80% and 120%. Maximal excretion rates of (S)-propranolol, (R)-propranolol, (S)-4'‑hydroxy propranolol, (R)-4'‑hydroxy propranolol, (S)-5'‑hydroxy propranolol, (R)-5'‑hydroxy propranolol, and (R)-7'‑hydroxy propranolol were 237 ng/min, 281 ng/min, 4 ng/min, 4 ng/min, 1 ng/min, 9 ng/min, and 3 ng/min, respectively.

中文翻译：

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二维色谱质谱：生物分析中普萘洛尔代谢中的手性位移定量。

在这项研究中，成功​​开发并优化了切割中心二维液相色谱方法，以区分和定量（S）-普萘洛尔，（R）-普萘洛尔及其羟基代谢物，即异构体（S）-4'-羟基普萘洛尔，（R）-4'-羟基普萘洛尔，（S）-5'-羟基普萘洛尔，（R）-5'-羟基普萘洛尔，（S）-7'-羟基普萘洛尔和（R）-7'-一次色谱运行中得到羟基普萘洛尔 因此，使实验研究普萘洛尔的环羟基化中的手性区分成为可能。在单次口服40 mg普萘洛尔后对人尿液样品的分析清楚地显示了普萘洛尔及其4'-，5'-和7'-羟基代谢产物发生了明显的手性变化。此外，在给药后24小时内连续监测各个（S）-和（R）-对映体的排泄速率。利用连接到三重四极杆质谱仪的2D-LC系统进行研究。色谱系统在第一维使用反相柱（苯基己基），在第二维使用基于替考拉宁的手性柱。该方法已基本验证并成功评估为鲁棒性。进行校准以达到80％至120％的精度。（S）-普萘洛尔，（R）-普萘洛尔，（S）-4'-羟基普萘洛尔，（R）-4'-羟基普萘洛尔，（S）-5'-羟基普萘洛尔，（R）- 5'-羟基普萘洛尔和（R）-7'-羟基普萘洛尔分别为237 ng / min，281 ng / min，4 ng / min，4 ng / min，1 ng / min，9 ng / min和3 ng / min。