Reproducibility and Quantification of Illicit Drugs Using Matrix-Assisted Ionization (MAI) Mass Spectrometry

Abstract

Matrix-assisted ionization (MAI) mass spectrometry (MS) is a simple and sensitive method for analysis of low- and high-mass compounds, requiring only that the analyte in a suitable matrix be exposed to the inlet aperture of an atmospheric pressure ionization mass spectrometer. Here, we evaluate the reproducibility of MAI and its potential for quantification using six drug standards. Factors influencing reproducibility include the matrix compound used, temperature, and the method of sample introduction. The relative standard deviation (RSD) using MAI for a mixture of morphine, codeine, oxymorphone, oxycodone, clozapine, and buspirone and their deuterated internal standards using the matrix 3-nitrobenzonitrile is less than 10% with either a Waters SYNAPT G2 or a Thermo LTQ Velos mass spectrometer. The RSD values obtained using MAI are comparable to those using ESI or MALDI on these instruments. The day-to-day reproducibility of MAI determined for five consecutive days with internal standards was better than 20% using manual sample introduction. The reproducibility improved to better than 5% using a mechanically assisted sample introduction method. Hydrocodone, present in a sample of undiluted infant urine, was quantified with MAI using the standard addition method.

High Sensitivity Analysis of Nanoliter Volumes of Volatile and Nonvolatile Compounds using Matrix Assisted Ionization (MAI) Mass Spectrometry

“…The MH + and MH 2 2+ ions, m/z 336 and m/z 168, respectively, appear well above background. As previously reported, the MAI method also works well using salty and buffered solutions [23,25,26]. This is demonstrated with Method 3 using a urine sample spiked with LSD to make a 1-ppm solution.…”

“…The syringe is mechanically guided by a x, y, z-stage. Excellent reproducibility provided quantitative results similar to ESI employing internal standards [25]. Using this approach, decreasing the volume of matrix:analyte solution to a fraction of 1 μL provided nearly comparable signal-to-noise as the 1 μL injection, somewhat similar to electrospraying at low flow rates in ESI.…”

Novel ionization processes for use in mass spectrometry: ‘Squeezing’ nonvolatile analyte ions from crystals and droplets

“…Consequently, using mass spectrometers optimized for ESI‐ and MALDI‐MS, the ease of adaptation of the methods based on the new ionization processes varies. It may only require turning off the high voltages and/or laser, or it may necessitate more significant physical modification(s) to obtain analytical useful results . As an example, the currently best performing MAI matrix, 3‐NBN, on Waters SYNAPT G2 and G2S instruments works exceptionally well for analyte ionization on the intermediate pressure MALDI sources without the use of the laser, but performs best at room temperature on the ESI Z‐Spray source blocks, and above the melting point of the matrix, 114–117 °C, the analyte ion abundance essentially ceases on this instrument .…”

“…A number of different mass spectrometers, in terms of analyzer types and vendors, have been used with the novel ionization processes demonstrating the importance of pressure, temperature, and collisions in optimizing ion formation . An example is shown in Figure for bovine serum albumin (BSA), 66 kDa, using mass spectrometers to ionize this 66 kDa protein intact and multiply charged using the new ionization processes.…”

“…By placing matrix only on the specific area(s) of interest on a surface and exposing the surface to the vacuum of the mass spectrometer, ions are observed from compounds exposed to the matrix solution, allowing rapid interrogation of ‘features of interest’ . The discoveries of these processes and development of suitable technologies were accomplished through fundamental research and using commercially available ion source inlets ’as is’ or with simple physical source modifications . Recently, we have begun to design and build dedicated inlets with the promise of a better understanding of the ionization processes and making improvements in applications .…”