Unni L K, Becker R E
Department of Psychiatry, Southern Illinois University School of Medicine, Springfield 62794-9230.
J Chromatogr. 1992 Jan 17;573(2):275-81. doi: 10.1016/0378-4347(92)80129-e.
An analytical method was developed with sensitivity to detect clinically significant concentrations of heptylphysostigmine (HP), a new physostigmine derivative with potent and long-lasting inhibitory activity on cholinesterase. HP, an experimental drug for Alzheimer disease, was measured in human plasma by high-performance liquid chromatography with electrochemical detection with use of a normal-phase column and acetonitrile buffer containing tetrahydrofuran and sodium acetate, pH 4.6. The limit of detection of the method was 0.125 ng/ml using a 2-ml sample of plasma. Analytical recovery of HP was 53.04 +/- 7.75% for plasma in the range 0.25-2.5 ng/ml. Stability studies conducted at 37 degrees C indicated that the drug was stable in 1 M hydrochloric acid, 1 M hydrogen peroxide and sodium acetate-buffered solution at pH 4 for at least 6 h but at pH 7 it degraded slightly to 79% at 6 h and was unstable in 1 M sodium hydroxide with only 9% of the parent compound remaining at 30 s. HP was stable when exposed to ultraviolet light at 22 degrees C or 100% relative humidity at 37 degrees C, with almost 80 and 75% of the parent compound remaining after 4 and 28 days, respectively. HP was stable in plasma at 4 degrees C for 0.25 h, and it slowly degraded to 56 and 28% of the original concentration by 1 and 2 h, respectively. HP was highly unstable in plasma at higher temperatures; at 22 and 37 degrees C it degraded immediately to 48 and 36% of the original concentration and was not detected after 0.5 and 0.25 h, respectively.
开发了一种分析方法，该方法具有检测临床显著浓度的庚基毒扁豆碱（HP）的灵敏度，HP是一种新的毒扁豆碱衍生物，对胆碱酯酶具有强大且持久的抑制活性。HP作为一种治疗阿尔茨海默病的实验性药物，采用正相柱和含有四氢呋喃及醋酸钠（pH 4.6）的乙腈缓冲液，通过高效液相色谱 - 电化学检测法在人血浆中进行测定。使用2 ml血浆样品时，该方法的检测限为0.125 ng/ml。对于0.25 - 2.5 ng/ml范围内的血浆，HP的分析回收率为53.04±7.75%。在37℃进行的稳定性研究表明，该药物在1 M盐酸、1 M过氧化氢和pH 4的醋酸钠缓冲溶液中至少6小时稳定，但在pH 7时，6小时后略有降解至79%，在1 M氢氧化钠中不稳定，30秒时仅剩下9%的母体化合物。HP在22℃暴露于紫外光或37℃相对湿度100%的条件下稳定，4天和28天后分别有近80%和75%的母体化合物残留。HP在4℃血浆中0.25小时内稳定，1小时和2小时后分别缓慢降解至原始浓度的56%和28%。HP在较高温度下在血浆中极不稳定；在22℃和37℃时分别立即降解至原始浓度的48%和36%，0.5小时和0.25小时后分别未检测到。
