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目的:研究血浆中华法林对映体的浓度对华法林抗凝疗效的影响。方法:建立血浆中华法林对映体浓度的立体选择性高效液相色谱法,采用手性-AGP色谱柱(ULTRON ES-OVM 5μm,150 mm×4.6 mm),保护柱(ULTRON ES-OVM.G 10mm×4.6 mm),以乙腈-20 mmol·L-1磷酸盐缓冲液(14∶86,p H 5)为流动相,流速1.0 m L·min-1,检测波长308 nm,柱温30℃,内标峰面积法定量计算。对146名心脏瓣膜置换术后使用华法林进行抗凝治疗的患者,服药后11~13 h按上述方法进行华法林对映体血浆浓度的检测。结果:1对映体标准曲线范围为75~2500 ng·m L-1,最低检出限为25 ng·m L-1,批内、批间RSD均在10%以下,回收率>90%,血浆样品稳定性良好。2R(+)-华法林平均血浆浓度为(635.0±380.7)ng·m L-1,S(-)-华法林平均血浆浓度为(334.8±237.7)ng·m L-1;S(-)-华法林血浆浓度与国际标准化比值(INR)值呈显著正相关(r=0.252,P<0.05),随着S(-)-华法林血浆浓度的升高,华法林的抗凝疗效增强,R(+)-华法林血浆浓度与INR值无显著相关性(r=0.104,P>0.05)。INR值在安全范围(1.8~3.0)的125例患者中,有92例(73.6%)S(-)-华法林血浆浓度在(334.8±237.7)ng·m L-1。结论:本研究建立的华法林对映体血浆浓度的检测方法灵敏而可靠,可作为华法林抗凝疗效的监测指标,联合INR值有助于提高抗凝监测的准确性。
OBJECTIVE: To study the effect of warfarin enantiomer concentration on warfarin anticoagulation in plasma. Methods: The enantioselectivity of warfarin in plasma was established by stereoselective HPLC with chiral-AGP column (ULTRON ES-OVM 5 μm, 150 mm × 4.6 mm) and guard column (ULTRON ES-OVM). G 10 mm × 4.6 mm) with a mobile phase of acetonitrile-20 mmol·L-1 phosphate buffer (14:86, p H 5) at a flow rate of 1.0 mL · min-1 and a detection wavelength of 308 nm with a column temperature of 30 ℃, internal standard peak area method for quantitative calculation. In 146 patients who underwent anticoagulant therapy with warfarin after heart valve replacement, the warfarin enantiomer plasma concentration was measured 11 to 13 hours after the administration as described above. Results: The standard curve of 1 enantiomer ranged from 75 to 2500 ng · m L-1, with the lowest detection limit of 25 ng · m L-1. The RSDs within and between batches were below 10% and the recoveries were above 90% , Plasma samples with good stability. The average plasma concentration of 2R (+) - warfarin was (635.0 ± 380.7) ng · m L-1 and the mean plasma concentration of S (-) - warfarin was 334.8 ± 237.7 ng · m L- -) - There was a significant positive correlation between warfarin plasma concentration and International Normalized Ratio (INR) (r = 0.252, P <0.05). With the increase of S (-) - warfarin plasma concentration, There was no significant correlation between R (+) - warfarin plasma concentration and INR value (r = 0.104, P> 0.05). Of the 125 patients with INR values within the safety range of 1.8 to 3.0, 92 (73.6%) had S (-) - warfarin plasma concentrations of 334.8 ± 237.7 ng · m L-1. CONCLUSION: The method for detecting the plasma concentration of warfarin enantiomers established in this study is sensitive and reliable and can be used as a monitoring indicator of warfarin anticoagulation efficacy. Combined with INR value, it is helpful to improve the accuracy of anticoagulation monitoring.