中文摘要：

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 mL·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·mL^-1,最低检出限为25 ng·mL^-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·mL^-1,S（-）-华法林平均血浆浓度为（334.8±237.7）ng·mL^-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·mL^-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。

英文摘要：

Objective： To study the influence of concentration of warfarin enantiomers in human plasma on warfarin anticoagulation. Methods： A stereo selective HPLC method was established to determine warfarin enantiomers in human plasma. The HPLC method employed the chiral- AGP column（ 150 mm × 4. 6 mm,5 μm） 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. The UV detection wavelength was 308 nm and the column temperature was 30 ℃. The internal standard peak area method for quantitative calculation was used. One hundred and forty- six Chinese patients after heart valve replacement（ HVR）receiving a long- term warfarin maintenance therapy participated in the study. Plasma concentration of warfarin enantiomers at post- dosing 11 to 13 hours were measured by means of the chiral HPLC. Results： ① The range of standard curve of each enantiomer was 75- 2500 ng·mL^-1,with the lowest limit of detection of 25 ng·mL^-1. RSDs of within or between- assay were less than 10% and the average recovery rate was 〉90%. Plasma samples has good stability. ②The mean concentration of R（ ＋）- and S（-）- warfarin in plasma were（ 635. 0 ± 380. 7） ng·mL^-1 and（ 334. 8 ± 237. 7） ng·mL^-1,respectively,indicating that a significant positive relationship between the international normalized ratio（ INR） and S（-）- warfarin plasma concentration（ r = 0. 252,P〈0. 05）. With the increase of S（-）- warfarin plasma concentration,the anticoagulant effect was enhanced. There was no significant correlation between R（ ＋）- warfarin plasma concentration with INR values（ r = 0. 104,P〉0. 05）. The results showed that the 125 cases had their INR within the safety range（ 1. 8- 3. 0）,of which 92（ 73. 6%） cases had a S（-）- warfarin level at（ 334. 8 ± 237. 7） ng·mL^-1. Conclusion： The method is sensitive and reliable. The plasma concentration of warfarin can serve as a sensitive index in monitoring anticoagulant