伊班膦酸钠,全世界用于治疗骨质疏松症的第三代二磷酸药物,具有使用方便的优点,低毒性,和显著的治疗效果。然而,伊班膦酸钠合成过程中残留的有机溶剂不仅对药物的疗效有负面影响,但也会导致药物稳定性下降。此外,如果这些溶剂的残留量超过安全标准,它们可能对人类健康构成严重威胁。本研究成功建立了一种简便、高效的顶空气相色谱法(HS-GC)同时测定5种残留溶剂(甲醇,丙酮,苯,甲苯,伊班膦酸钠原料中的1-戊醇)。结果表明,使用DB-624毛细管柱(30m×0.32mm×1.8μm)和火焰电离检测器,结合顶空自动采样和温度程序,可以获得令人满意的分析性能。具体操作条件包括40℃的初始温度,保持2分钟,然后首先以5℃/min的速率升温至200℃,然后以20℃/min的速率升温至240℃,保持5分钟。使用流量为1mL/min,分流比为14∶1的氮气作为载气。顶部空间小瓶温度保持在80℃,样品平衡时间为20分钟。在既定的分析条件下,甲醇的质量浓度(72-216μg/mL)之间具有良好的线性关系,丙酮(120-360μg/mL),苯(0.048-0.144μg/mL),甲苯(21.36-64.08μg/mL),和1-戊醇(120-360μg/mL)及其相应的峰面积,相关系数(r)大于0.990。这些溶剂的检出限为2.88、0.011、0.90、0.24和0.024ng/mL,分别,定量限为11.5、0.043、3.6、0.96和0.096ng/mL,分别。此外,这些溶剂的回收率为86.3%至101.9%,具有相对标准偏差(RSD,n=3)小于2.49%。该方法简单,准确,可靠,适用于伊班膦酸钠原料中5种残留溶剂的快速同时测定。本研究对提高药品安全性、保障公众健康具有重要的现实意义。
Ibandronate sodium, a third-generation diphosphate drug used worldwide to treat osteoporosis, has the advantages of convenient use, low toxicity, and significant therapeutic effects. However, the residual organic solvents in the synthesis process of sodium ibandronate not only have a negative impact on the efficacy of the drug, but also lead to a decrease in drug stability. Moreover, if the residual amounts of these solvents exceed safety standards, they may pose serious threats to human health. This study successfully established a convenient and efficient method based on headspace-gas chromatography (HS-GC) for the simultaneous determination of five residual solvents (methanol, acetone, benzene, toluene, 1-pentanol) in the raw materials of ibandronate sodium. The results indicated that satisfactory analytical performance can be achieved by using DB-624 capillary column (30 m×0.32 mm×1.8 μm) and a flame ionization detector in conjunction with headspace autosampling and a temperature program. The specific operating conditions included an initial temperature of 40 ℃, with a hold of 2 min, followed by a temperature ramp first to 200 ℃ at a rate of 5 ℃/min and then to 240 ℃ at a rate of 20 ℃/min, with a hold of 5 min. Nitrogen with a flow rate of 1 mL/min and split ratio of 14∶1 was used as the carrier gas. The headspace vial temperature was maintained at 80 ℃, and the sample equilibration time was 20 min. Under the established analytical conditions, good linear relationships were obtained between the mass concentrations of methanol (72-216 μg/mL), acetone (120-360 μg/mL), benzene (0.048-0.144 μg/mL), toluene (21.36-64.08 μg/mL), and 1-pentanol (120-360 μg/mL) and their corresponding peak areas, with correlation coefficients (r) greater than 0.990. The limits of detection for these solvents were 2.88, 0.011, 0.90, 0.24, and 0.024 ng/mL, respectively, with limits of quantification of 11.5, 0.043, 3.6, 0.96, and 0.096 ng/mL, respectively. Furthermore, the recoveries of these solvents ranged from 86.3% to 101.9%, with relative standard deviations (RSDs, n=3) of less than 2.49%. The proposed method is simple, accurate, reliable, and suitable for the rapid and simultaneous determination of five residual solvents in the raw materials of ibandronate sodium. This study has important practical significance in improving drug safety and ensuring public health.