International Journal for Ion Mobility Spectrometry

Electrospray ionization (ESI) is an important tool in chemical and biochemical survey and targeted analysis in many applications. For chemical detection and identification electrospray is usually used with mass spectrometry (MS). However, for screening and monitoring of chemicals of interest in light, low power field-deployable instrumentation, an alternative detection technology with chemical selectivity would be highly useful, especially since small, lightweight, chip-based gas and liquid chromatographic technologies are being developed. Our initial list of applications requiring portable instruments includes chemical surveys on Mars, medical diagnostics based on metabolites in biological samples, and water quality analysis. In this report, we evaluate ESI-Differential Mobility Spectrometry (DMS) as a compact, low-power alternative to MS detection. Use of DMS for chemically-selective detection of ESI suffers in comparison with mass spectrometry because portable MS peak capacity is greater than that of DMS by 10X or more, but the development of light, fast chip chromatography offers compensating resolution. Standalone DMS provides the chemical selectivity familiar from DMS-MS publications, and exploits the sensitivity of ion detection. We find that sub-microliter-per-minute flows and a correctly-designed interface prepare a desolvated ion stream that enables DMS to act as an effective ion filter. Results for a several small organic biomarkers and metabolites, including citric acid, azelaic acid, n­hexanoylglycine, thymidine, and caffeine, as well as compounds such as dinitrotoluene and others, have been characterized and demonstrate selective detection. Water-quality-related halogen-containing anions, fluoride through bromate, contained in liquid samples are also isolated by DMS. A reaction-chamber interface is highlighted as most practical for portable ESI-DMS instrumentation.

The paper presents the results of studying the system of a liquid chromatograph (LC) coupling with an ion-mobility spectrometer (IMS) with orthogonal electrostatic deflection of ions obtained by the electrospray method at high flow rates of the liquid under analysis (200 to 300 microL/min), which ensures stable operation of the LC/IMS analytical setup without separating the liquid flow leaving the liquid chromatograph column.

Tăng cường chiều của một phân tích cho phép khảo sát chi tiết và toàn diện hơn về các hỗn hợp phức tạp. Các kỹ thuật tách đơn chiều như sắc ký khí (GC) và phổ động lực ion (IMS) cung cấp thông tin hóa học hạn chế về các hỗn hợp phức tạp. Sự kết hợp giữa GC, phổ động lực ion và phổ khối thời gian bay (GC-IM-TOFMS) cung cấp tách ba chiều cho các hỗn hợp phức tạp. Trong nghiên cứu này, một hệ thống GC-IM-TOFMS lai với nguồn ion hóa phun tĩnh điện thứ cấp (SESI) đã cung cấp bốn loại thông tin phân tích: thời gian giữ GC, thời gian trôi ion động học, tỷ lệ khối lượng lên điện tích và cường độ ion. Việc sử dụng ion hóa phun tĩnh điện thứ cấp cho phép ion hóa hiệu quả và nhẹ nhàng các hơi mẫu khí ở áp suất khí quyển. Nhiều hỗn hợp phức tạp, bao gồm tinh dầu hoa oải hương và bạc hà, đã được phân tích bằng GC-SESI-IM-TOFMS. Dữ liệu 3D thu được từ những hỗn hợp này, mỗi mẫu chứa hơn 50 thành phần, đã được vẽ dưới dạng hình chiếu 3D. Đặc biệt, dữ liệu đã xử lý sau đó được vẽ trong ba chiều cho thấy rằng nhiều đỉnh GC đã được chọn khối lượng đã được phân giải thành các đỉnh ion động lực khác nhau. Kỹ thuật này cho thấy rõ tiềm năng cho các phân tích sâu hơn về các hỗn hợp hóa học và sinh học phức tạp.

Exhaled breath of patients suffering non-small bronchial carcinoma contains volatile organic compounds (VOC) different from healthy people. VOCs could be detected using ion mobility spectrometry down to the pg/L range even in air directly. To date, the origin of the different VOCs found is insecure. Such VOCs could be a direct product of the metabolism of the tumor or relatable to mostly present co-factors like infections or necrosis or a reaction of the human organism to the tumor (e.g. oxidativ stress). In the present study the breath of 19 patients suffering from confirmed NSCLC (non-small-cell lung carcinoma) with different histological types was investigated. In all cases flexible video-chip bronchoscopy was realized. Before taking samples for histological investigations in the lung on both main bronchi, samples of air were taken using a polytetrafluoroethylene (PTFE or Teflon) tube as catheter directly from the working channel of a bronchoscope and connected directly to the inlet of the ion mobility spectrometer. The measurement was started immediately. In total, 72 common peaks could be identified. 5 Peaks were significantly varying between the tumor site and the collateral lung. Considering adenocarcinoma, one peak separates both sites clearly and was relatable to the dimer of n-Dodecane. Two peaks were found on squamous cell carcinoma and relatable to 2-Butanol or 2-Methylfuran and Nonanal. The sensitivity, specificity, positive and negative predictive values were, for adenocarcinoma 100%, 75%, 80% and 100%, respectively – for squamous cell carcinoma 78%/78%, 67%/78%, 70%/80% and 75%/88%, for 2-Butanol and Nonanal respectively. Therefore, VOCs obtained from bronchoscopic sampling of breath could be detected using ion mobility spectrometry. The present study suggests that lung carcinoma with different histology will be represented by different volatile analytes.

In vivo drug metabolism studies with low concentrations of analytes and high matrix burden are challenging. Of special interest are ‘first-in-man’ studies in early stages of pharmaceutical development that do not use 14C labeled drug candidates. Beside conventional MS-fishing techniques which are biased towards known/expected metabolites and mass defect filtration procedures, this paper focuses on the untargeted/unbiased analysis of drug related compounds in complex matrices using two orthogonal separation techniques: UPLC and TWIMS. Standard sample material after oral administration of a drug compound to rats was investigated by UPLC/TWIMS in MSE acquisition mode using interlaced collision energies for the parallel detection of [M+H]+ parent ions and fragments. Due to the fragmentation after ion mobility separation in the transfer region of the Synapt G2-triwave device, [M+H]+ ion species are aligned with their related fragments by virtue of possessing the same retention time and drift time profile. Four dimensional data analysis of the continuum raw data was performed by automated peak picking and alignment within the MSE viewer software. As result, completely purified MS- and MS/MS-data of metabolites were extracted from raw mass data with high matrix burden and were used without compromise for structure elucidation. This analytical methodology is universally applicable for the unbiased/untargeted and robust analysis of any analyte of interest in complex matrices, including small molecules, peptides and proteins. The high quality data files can be used as data repositories for the purpose of retrospective analysis which is of particular interest for the long term process in drug development.