高效液相色谱-电喷雾电离串联质谱法测定犬和马血浆中利多卡因及其两种N-去乙基代谢物
Determination of lidocaine and its two N-desethylated metabolites in dog and horse plasma by high-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry.
作者信息
Maes A, Weiland L, Sandersen C, Gasthuys F, De Backer P, Croubels S
机构信息
Department of Pharmacology, Toxicology, Biochemistry and Organ Physiology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
出版信息
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jun 1;852(1-2):180-7. doi: 10.1016/j.jchromb.2007.01.010. Epub 2007 Jan 18.
A sensitive method for the quantification of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in animal plasma using high-performance liquid chromatography combined with electrospray ionization mass spectrometry is described. The sample preparation includes a liquid-liquid extraction with methyl tert-butylmethyl ether after addition of 2M sodium hydroxide. Ethylmethylglycinexylidide (EMGX) is used as an internal standard. For chromatographic separation, an ODS Hypersil column was used. Isocratic elution was achieved with 0.01 M ammonium acetate and acetonitrile as mobile phases. Good linearity was observed in the range of 2.5-1000 ng ml(-1) for lidocaine in both dog and horse plasma. For MEGX, linear calibration curves were obtained in the range of 5-1000 ng ml(-1) and 20-1000 ng ml(-1) for dog and horse plasma, respectively. In dog and horse plasma good linearity was observed in the range of 200-1500 ng ml(-1) for GX. The limit of quantification (LOQ) in dog plasma for lidocaine, MEGX and GX was set at 2.5 ng ml(-1), 20 ng ml(-1) and 200 ng ml(-1), respectively. For horse plasma a limit of quantification of 2.5 ng ml(-1), 5 ng ml(-1) and 200 ng ml(-1) was achieved for lidocaine, MEGX and GX, respectively. In dog plasma, the limit of detection (LOD) was found to be 0.8 ng ml(-1), 2.3 ng ml(-1) and 55 ng ml(-1) for lidocaine, MEGX and GX, respectively. In horse plasma the LOD's found for lidocaine, MEGX and GX, were 1.1 ng ml(-1), 0.5 ng ml(-1) and 13 ng ml(-1), respectively. The method was shown to be of use in pharmacokinetic studies after application of a transdermal patch in dogs and after an intravenous infusion in horses.
描述了一种使用高效液相色谱结合电喷雾电离质谱法对动物血浆中利多卡因及其代谢物单乙基甘氨酰二甲苯胺（MEGX）和甘氨酰二甲苯胺（GX）进行定量的灵敏方法。样品制备包括在加入2M氢氧化钠后用甲基叔丁基甲醚进行液 - 液萃取。乙基甲基甘氨酰二甲苯胺（EMGX）用作内标。色谱分离使用ODS Hypersil柱。以0.01M醋酸铵和乙腈作为流动相实现等度洗脱。在犬和马血浆中，利多卡因在2.5 - 1000 ng ml⁻¹范围内观察到良好的线性。对于MEGX，在犬血浆和马血浆中分别在5 - 1000 ng ml⁻¹和20 - 1000 ng ml⁻¹范围内获得线性校准曲线。在犬和马血浆中，GX在200 - 1500 ng ml⁻¹范围内观察到良好的线性。犬血浆中利多卡因、MEGX和GX的定量限（LOQ）分别设定为2.5 ng ml⁻¹、20 ng ml⁻¹和200 ng ml⁻¹。对于马血浆，利多卡因、MEGX和GX的定量限分别为2.5 ng ml⁻¹、5 ng ml⁻¹和200 ng ml⁻¹。在犬血浆中，利多卡因、MEGX和GX的检测限（LOD）分别为0.8 ng ml⁻¹、2.3 ng ml⁻¹和55 ng ml⁻¹。在马血浆中，利多卡因、MEGX和GX的检测限分别为1.1 ng ml⁻¹、0.5 ng ml⁻¹和13 ng ml⁻¹。该方法在犬应用透皮贴剂后和马静脉输注后被证明可用于药代动力学研究。
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