Padrini R, Piovan D, Gaglione E, Zordan R, Ferrari M
Department of Pharmacology, University of Padua, Italy.
Ther Drug Monit. 1992 Oct;14(5):391-6. doi: 10.1097/00007691-199210000-00009.
Lorajmine is a monochloroacetyl derivative of ajmaline with electrophysiological properties somewhat different from those of the compound of origin. Since lorajmine is rapidly hydrolyzed to ajmaline by plasma and tissue esterases, it is crucial to measure plasma levels of both drugs separately. A major problem in assaying lorajmine is its chemical instability in plasma both after blood sampling and during the extraction procedure. Furthermore, lorajmine (unlike ajmaline) is not fluorescent and has a very low UV absorbance, so the standard detectors for high-performance liquid chromatography cannot be used. We describe a new method that solves the problems of instability and sensitivity. Plasma esterases are first blocked pharmacologically (neostigmine); ajmaline is then measured by direct on-column injection of samples. Last, lorajmine is completely converted to ajmaline, extracted, and measured with a fluorescence detector. The molar concentration of ajmaline obtained in the last step, minus that found by direct injection, gives the concentration of lorajmine. Some examples of pharmacokinetic applications are also given.
劳卡尼是阿义马林的一氯乙酰衍生物，其电生理特性与母体化合物略有不同。由于劳卡尼会被血浆和组织酯酶迅速水解为阿义马林，因此分别测定两种药物的血浆水平至关重要。测定劳卡尼的一个主要问题是其在采血后及提取过程中在血浆中的化学不稳定性。此外，劳卡尼（与阿义马林不同）无荧光且紫外吸收极低，因此不能使用高效液相色谱的标准检测器。我们描述了一种新方法，该方法解决了不稳定性和灵敏度问题。首先通过药理学方法（新斯的明）阻断血浆酯酶；然后通过直接进样测定阿义马林。最后，将劳卡尼完全转化为阿义马林，进行提取并用荧光检测器测定。最后一步得到的阿义马林的摩尔浓度减去直接进样测得的浓度，即为劳卡尼的浓度。文中还给出了一些药代动力学应用的实例。
