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首页> 外文期刊>Chromatographia >Enantioselective Separation and Determination of Carnosine in Rat Plasma by Fluorescence LC for Stereoselective Pharmacokinetic Studies
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Enantioselective Separation and Determination of Carnosine in Rat Plasma by Fluorescence LC for Stereoselective Pharmacokinetic Studies

机译：对映体分离和测定大鼠血浆中肌肽的荧光LC，用于立体选择性药代动力学研究

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A sensitive fluorescence liquid chromatographic analytical method was developed for the simultaneous determination of carnosine enantiomers in rat plasma. The method was applied to pharmacokinetic studies. Chiral separation of carnosine enantiomers was achieved by pre-column derivatization with o-phthaldialdehyde and the thiol N-acety-l-cysteine as derivating reagents. They were separated on an ODS column and detected by fluorescence detection (λex = 350 nm, λem = 450 nm). γ-Aminobutyric acid was used as internal standard. The method was linear up to 6,000 ng mL−1 for l-carnosine, 4,000 ng mL−1 for d-carnosine. Low limit of quantitation (LLOQ) was 40 ng mL−1 for each isomer. The relative standard deviations obtained for intra- and inter-day precision were lower than 12% and the recoveries were higher than 75% for both enantiomers. The method was applied to a stereoselective study on the pharmacokinetics of carnosine after oral administration with a single dose (carnosine, 75 mg kg−1 for each isomer) to a rat. The initial data indicated that l-carnosine had a larger value of the highest plasma concentration than d-carnosine (C max 5,344 vs. 1,914 ng mL−1), and that of l-carnosine had a lower value of AUC(0−∞) and t 1/2(h) (AUC(0−∞) 5,306 vs. 6,321 ng h mL−1, t 1/2 1.43 vs. 3.37 h). Our results indicated that the pharmacokinetic of l-carnosine and d-carnosine revealed enantioselective properties significantly.
机译：建立了灵敏的荧光液相色谱分析方法，用于同时测定大鼠血浆中的肌肽对映体。该方法被应用于药代动力学研究。肌肽对映体的手性分离是通过用邻苯二甲醛和硫醇N-乙酰-1-半胱氨酸作为衍生试剂进行柱前衍生而实现的。将它们在ODS柱上分离并通过荧光检测（λ ex = 350 nm，λ em = 450 nm）进行检测。 γ-氨基丁酸用作内标。该方法是线性的，对左旋肌氨酸为6,000 ng mL -1 ，对d-肌氨酸为4,000 ng mL -1 。每种异构体的定量下限（LLOQ）为40 ng mL -1 。两种对映异构体的日内和日间精度所获得的相对标准偏差均低于12％，回收率高于75％。该方法用于对大鼠单剂量口服肌肽（肌肽，每种异构体75 mg kg -1 ）后肌肽的药代动力学的立体选择性研究。初始数据表明，左旋肌肽的最高血浆浓度值大于右旋肌氨酸（C max 5,344对1,914 ng mL -1 ），并且肌肽的AUC （0-∞）和t 1/2（h）（AUC （0-∞） > 5,306 vs. 6,321 ng h mL −1 ，t 1/2 1.43 vs. 3.37 h）。我们的结果表明，左旋肌肽和右旋肌氨酸的药代动力学显着揭示了对映选择性。

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