加压素V_2受体拮抗剂Lixivaptan

低钠血症系指患者体内血清Na＋水平低于135mmol.L-1的一种电解质异常表现,可由多种疾病,如抗利尿激素分泌不当综合征（SIADH）、心衰、肝硬化等引起。目前临床治疗药物,如限制性补液、利尿剂和去甲基金霉素分别因存在依从性差、

Hyponatremia in patients with heart failure

The present review analyses the mechanisms relating heart failure and hyponatremia,describes the association of hyponatremia with the progress of disease and morbidity/mortality in heart failure patients and presents treatment options focusing on the role of arginine vasopressin(AVP)-receptor antagonists.Hyponatremia is the most common electrolyte disorder in the clinical setting and in hospitalized patients.Patients with hyponatremia may have neurologic symptoms since low sodium concentration produces brain edema,but the rapid correction of hyponatremia is also associated with major neurologic complications.Patients with heart failure often develop hyponatremia owing to the activation of many neurohormonal systems leading to decrease of sodium levels.A large number of clinical studies have associated hyponatremia with increased morbidity and mortality in patients hospitalized for heart failure or outpatients with chronic heart failure.Treatment options for hyponatremia in heart failure,such as water restriction or the use of hypertonic saline with loop diuretics,have limited efficacy.AVP-receptor antagonists increase sodium levels effectively and their use seems promising in patients with hyponatremia.However,the effects of AVP-receptor antagonists on hard outcomes in patients with heart failure and hyponatremia have not been thoroughly examined.

用液相色谱-串联质谱法检测人尿中三种普坦类兴奋剂控制药物

目的：建立使用液相色谱一串联质谱（LC—MS／MS）同时测定尿样中三种普坦类药物（托伐普坦、考尼伐坦和利希普坦）的方法。方法：样品用5％乙酸铅水溶液沉淀蛋白质并离心后．在电喷雾正离子模式下，以多反应监测（MRM）方式采集数据进行定性和定量分析。结果：托伐普坦、考尼伐坦、利希普坦的最低检测限（LOD）分别为15ng／mL、1ng／mL和2ng／mL，线性范围（r2〉0．99）分别为45～3000、3～2000和6，400ng／mL。3种药物在低、中、高3个浓度水平下，日内变异系数均小于8．2％，日间变异系数均小于13．6％．检测的准确度大于90％。结论：该方法具有样品前处理简单、检测快捷、灵敏度高、重现性好、定性定量准确等特点，已用于我们实验室的兴奋剂控制样品常规检测中。

利希普坦的合成

2-氯-4-硝基苯甲酸经酯化、水合肼还原所得4-氨基-2-氯苯甲酸甲酯,与5-氟-2-甲基苯甲酰氯经酰化、水解及酰氯化反应制得2-氯-4-[(5-氟-2-甲基苯甲酰基)氨基]苯甲酰氯,再与10,11-二氢-5H-吡咯并[2,1-c][1,4]苯并二氮反应制得选择性精氨酸加压素V2受体拮抗剂利希普坦,总收率约57%(以2-氯-4-硝基苯甲酸计)。