Study Of Paper Spray Ionization Source In The Analysis Of Therapeutic Drugs

Paper spray ionization has been widely applied in the analysis of foodstuffs, pharmacetical drugs and biological samples due to its facile operation, high efficiency and low-cost. However, in a paper spray analysis the analytes are difficult to be eluted off in a short time resulting from the strong hydrogen bond and van der Waals interactions between the hydroxyl groups at the surface of paper substrate and polar groups in analytes. In order to decrease the interactions between paper substrate and analytes and improve the analysis sensitivity of paper spray ionization, a variety of inorganic compounds, including alumina/ aluminum hydroxide gel, aluminum nitrate and silica/silica gel were used to modify the surface of paper substrate in this thesis, and the obtained conclusions are as follows:(1)A variety of methods such as surface brushing, dipping and drop-cast were used to modify the surface of paper substrate,. The results showed that in comparison with the unmodified paper substrates, the analysis sensitivity using the modified paper substrates by alumina and aluminum hydroxide gel was not significantly improved in the analysis of drugs spiked in dired blood spots.(2)When the paper substrate was treated with a process by first impregnated with aluminum nitrate solution followed by baking, the analysis sensitivity improved around 4-fold and the limit of quantitation for the target drugs in dried blood spots reduced about 20-fold relative to those from the unmodified papers. For example, the limit of quantitation of amitriptyline and verapamil reduced from 10 ng/m L to 0.5 ng/m L by using the modified paper. Although such an improvement, the obtained paper substrates with the above method were brittle due to the decomposition of aluminum nitrate and the surface carbonization of paper substrates in the baking, not favoring the general operation.(3)When the paper substrates were, respectively, treated with sodium silicate solution and nitric acid solution, the resulting papers would make the analysis sensitivity improve around 3-fold relative to that without treated paper substrates. Moreover, the obtained papers have the characteristics of uniform surface structure and good reproducibility.(4)In the present investigation, the performance of different paper substrates including silica coated paper, Whatman Grade ET31 and Grade 1 papers were studies in detail. The results demonstrated that the limit of quantitation has been improved around 10 – 100-fold with the silica coated paper relative to those from Grade ET31 and Grade 1 papers. The reasons could be ascribed to the silica particles at the surface of silica coated paper, which to a large extend prevented the penetration of the spotted blood through the whole paper substrate. As a result, the target samples stayed at the surface of the silica coated paper, leading to a high elution efficiency after applying the spray solvent and favorable ionization performance.In summary, a variety of inorganic materials were employed to modify the paper surface, and some methods for modifying paper surfaces were developed. The obtained paper substrates were successfully used in paper spray ionization source for rapid analysis of different kinds of pharmaceutical drugs in complex sample matrices. The present study provides a new insight into the detection of target compounds in real samples with high sensitivity and throughput.