Biomedical Engineering Reference
In-Depth Information
The distribution of ATP (negative ion acquisition) in the tumor xenografts was also
studied and indicated that the cytotoxic metabolite AQ4 was confined to hypoxic
regions of the tumor as intended.
4.3
Application to Pharmaceutical Drug Formulation
Earnshaw et al. [
159
] recently used MALDI-MS to directly analyze a range of com-
mercially available and prescription tablet formulations, including aspirin, paraceta-
mol, sildenafil citrate (Viagra), and a batch of tablets in development. The tablet
sections approximately 1 mm in thickness were created by using a tablet cutter to
fracture the tablet if it is necessary. The exposed surface of the tablet was coated
with 25 mg/mL CHCA in EtOH containing 0.1 % TFA by an airspray. MALDI-MS
acquired data with MS full scan function. Drugs were clearly observed both in the
MS spectra and in the images as protonated molecules, or as sodium adducts.
MALDI-MS imaging also provided semiquantitative information.
5
Conclusion
Since its inception about 15 year ago, MALDI-IMS has been developed into a pow-
erful and versatile tool for biomedical research. It allows for the investigation of the
spatial distribution of molecules at complex surfaces. The combination of molecular
speciation with local analysis makes a chemical microscope that can be used for the
direct biomolecular characterization of histological tissue section surface. However,
successful detection of the analytes of interest at the desired spatial resolution
requires careful attention to several steps in the IMS protocol: matrix selection,
matrix coating, data acquisition, and data processing. MALDI-IMS is increasingly
playing an important role in the drug discovery and development and disease
treatment.
References
1. Fenn J, Mann M, Meng C, Wong S, Whitehouse C (1989) Electrospray ionization for mass
spectrometry of large biomolecules. Science 246:64-71. doi:10.1126/science.2675315
2. Karas M, Bachmann D, Hillenkamp F (1985) Influence of the wavelength in high-irradiance
ultraviolet laser desorption mass spectrometry of organic molecules. Anal Chem 57:2935-
2939. doi:10.1021/ac00291a042
3. Karas M, Hillenkamp F (1988) Laser desorption ionization of protein with molecular masses
exceeding 10000 Daltons. Anal Chem 60:2299-2301. doi:10.1021/ac00171a028
4. Tanaka K, Waki H, Ido Y, Akita S, Yoshida Y, Yoshida T (1988) Protein and polymer analysis
up to m/z 100000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass
Spectrom 2:151-153. doi:10.1002/rcm.1290020802
