KU Leuven - University of Leuven, Department of Pharmaceutical and Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, 3000, Leuven, Belgium.
KU Leuven - University of Leuven, Department of Pharmaceutical and Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, 3000, Leuven, Belgium.
J Pharm Biomed Anal. 2018 May 10;153:193-198. doi: 10.1016/j.jpba.2018.02.047. Epub 2018 Feb 23.
Traditional headspace - gas chromatography (HS-GC) methods for the determination of residual solvents (RS) start from a homogenous sample solution. Subsequently, it is challenging to determine RS using HS-GC techniques from insoluble solid samples like gelatin which is practically impossible to dissolve or distribute uniformly in water and common organic solvents. In this study, a thermal desorber combined with capillary gas chromatography and flame ionization detection/mass spectrometry (TD-GC-FID/MS) was used for quantitative determination of residual dimethylsulfoxide (DMSO) in gelatin without sample pretreatment. A sample of gelatin was sandwiched between two quartz filter double layers in a polytetrafluoroethylene insert which was then placed in its entirety into a thermal desorption tube. Factors affecting the performance of TD-GC including desorption time, desorption temperature, desorption flow and type of adsorbent were studied by applying a standard solution of DMSO in methanol on a blank gelatin bed. Validation results of the proposed method showed good linearity with an R-value higher than 0.999 for a wide concentration range and good sensitivity with a limit of detection and limit of quantification of 0.1 μg and 0.2 μg on tube, respectively. The proposed method shows recovery values close to 100%. In addition, a conventional HS-GC method following enzymatic degradation of gelatin was developed to verify the proposed TD-GC method. Both methods were applied for the determination of residual DMSO in gelatin that was loaded with an experimental drug. Results were comparable, but the enzyme assisted HS-GC method was more time consuming and expensive.
传统的顶空-气相色谱（HS-GC）方法用于测定残留溶剂（RS）时，起始于均相样品溶液。然而，对于像明胶这样的不溶性固体样品，使用 HS-GC 技术来测定 RS 是具有挑战性的，因为明胶几乎不可能溶解或均匀分布在水和常见有机溶剂中。在本研究中，使用热解吸器结合毛细管气相色谱和火焰离子化检测/质谱（TD-GC-FID/MS），无需样品预处理即可定量测定明胶中的残留二甲基亚砜（DMSO）。将明胶样品夹在两个石英滤双层之间的聚四氟乙烯插片中，然后将其整体放入热解吸管中。通过在空白明胶床上用甲醇中的 DMSO 标准溶液施加影响 TD-GC 性能的因素，包括解吸时间、解吸温度、解吸流量和吸附剂类型。所提出方法的验证结果表明，在较宽的浓度范围内具有良好的线性，R 值高于 0.999，并且具有良好的灵敏度，管上的检测限和定量限分别为 0.1μg 和 0.2μg。该方法的回收率接近 100%。此外，还开发了一种传统的 HS-GC 方法，通过明胶的酶解来验证所提出的 TD-GC 方法。两种方法均用于测定加载实验药物的明胶中的残留 DMSO。结果是可比的，但酶辅助 HS-GC 方法更耗时且昂贵。
