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Mass Spectrometry Imaging of Pharmaceuticals: From Tablets to Tissues

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Analytical Techniques in the Pharmaceutical Sciences

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

Drug efficacy is dependent upon effective and controlled release for delivery to the target site. The properties of a drug product effecting delivery are carefully manipulated by a variety of ingredients/excipients serving various purposes. As such, there is high dependence on the optimal construction and spatial arrangement of all ingredients. The subsequent fate of the active pharmaceutical ingredient then ultimately determines therapeutic and toxic effects. Mass spectrometry imaging offers high sensitivity, specificity, high mass resolution and high mass ranges for imaging component distributions in solid forms and in biological tissues. This chapter reviews mass spectrometry imaging techniques most commonly utilised in these research areas. Examples are then provided of imaging various components in solid form products and on the exciting area of label-free imaging of pharmaceuticals and metabolites in animal tissues. A small section is also provided on micro-array imaging of biologicals. Due to the relative immaturity of the field, a special focus on future perspectives and emerging potential concludes the chapter.

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References

  • Ait-Belkacem R, Sellami L, Villard C, DePauw E, Calligaris D, Lafitte D (2012) Mass spectrometry imaging is moving toward drug protein co-localization. Trends Biotechnol 30(9):466–474

    Article  CAS  PubMed  Google Scholar 

  • Al-Bataineh SA, Short RD (2014) Protein patterning on microplasma-activated PEO-like coatings. Plasma Processes Polym 11(3):263–268

    Article  CAS  Google Scholar 

  • Braun RM, Beyder A, Xu J, Wood MC, Ewing AG, Winograd N (1999) Spatially resolved detection of attomole quantities of organic molecules localized in picoliter vials using time-of-flight secondary ion mass spectrometry. Anal Chem 71(16):3318–3324

    Article  CAS  PubMed  Google Scholar 

  • Brito E, Abreu S, Brien C, Skinner W (2010) ToF-SIMS as a new method to determine the contact angle of mineral surfaces. Langmuir 26(11):8122–8130

    Article  Google Scholar 

  • Brulet M, Seyer A, Edelman A, Brunelle A, Fritsch J, Ollero M, Laprévote O (2010) Lipid mapping of colonic mucosa by cluster TOF-SIMS imaging and multivariate analysis in cftr knockout mice. J Lipid Res 51(10):3034–3045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bugay DE (2001) Characterization of the solid-state: spectroscopic techniques. Adv Drug Del Rev 48(1):43–65

    Article  CAS  Google Scholar 

  • Bunch J, Clench MR, Richards DS (2004) Determination of pharmaceutical compounds in skin by imaging matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun Mass Spectrom 18(24):3051–3060

    Article  CAS  PubMed  Google Scholar 

  • Chan JGY, Chan HK, Prestidge CA, Denman JA, Young PM, Traini D (2013) A novel dry powder inhalable formulation incorporating three first-line anti-tubercular antibiotics. Eur J Pharm Biopharm 83(2):285–292

    Article  CAS  PubMed  Google Scholar 

  • Chughtai K, Heeren RMA (2010) Mass spectrometric imaging for biomedical tissue analysis. Chem Rev 110(5):3237–3277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Earnshaw CJ, Carolan VA, Richards DS, Clench MR (2010) Direct analysis of pharmaceutical tablet formulations using matrix-assisted laser desorption/ionisation mass spectrometry imaging. Rapid Commun Mass Spectrom 24(11):1665–1672

    Article  CAS  PubMed  Google Scholar 

  • Eijkel GB, KaletaÅŸ BK, Van Der Wiel IM, Kros JM, Luider TM, Heeren RMA (2009) Correlating MALDI and SIMS imaging mass spectrometric datasets of biological tissue surfaces. Surf Interface Anal 41(8):675–685

    Article  CAS  Google Scholar 

  • Finnskog D, Ressine A, Laurell T, Marko-Varga G (2004) Integrated protein microchip assay with dual fluorescent- and MALDI read-out. J Proteome Res 3(5):988–994

    Article  CAS  PubMed  Google Scholar 

  • Fisher GL, Belu AM, Mahoney CM, Wormuth K, Sanada N (2009) Three-dimensional time-of-flight secondary ion mass spectrometry imaging of a pharmaceutical in a coronary stent coating as a function of elution time. Anal Chem 81(24):9930–9940

    Article  CAS  PubMed  Google Scholar 

  • Fournier I, Wisztorski M, Salzet M (2008) Tissue imaging using MALDI-MS: a new frontier of histopathology proteomics. Expert Rev Proteomics 5(3):413–424

    Article  CAS  PubMed  Google Scholar 

  • Galhena AS, Harris GA, Nyadong L, Murray KK, Fernández FM (2010) Small molecule ambient mass spectrometry imaging by infrared laser ablation metastable-induced chemical ionization. Anal Chem 82(6):2178–2181

    Article  CAS  PubMed  Google Scholar 

  • Goodwin RJA, Iverson SL, Andren PE (2012) The significance of ambient-temperature on pharmaceutical and endogenous compound abundance and distribution in tissues sections when analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging. Rapid Commun Mass Spectrom 26(5):494–498

    Article  CAS  PubMed  Google Scholar 

  • Grey AC, Schey KL (2009) Age-related changes in the spatial distribution of human lens α-crystallin products by MALDI imaging mass spectrometry. Invest Ophthalmol Vis Sci 50(9):4319–4329

    Article  PubMed  PubMed Central  Google Scholar 

  • Gusev AI, Vasseur OJ, Proctor A, Sharkey AG, Hercules DM (1995) Imaging of thin-layer chromatograms using matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem 67(24):4565–4570

    Article  CAS  Google Scholar 

  • Harris GA, Nyadong L, Fernandez FM (2008) Recent developments in ambient ionization techniques for analytical mass spectrometry. Analyst 133(10):1297–1301

    Article  CAS  PubMed  Google Scholar 

  • Heeren RMA, Smith DF, Stauber J, Kükrer-Kaletas B, MacAleese L (2009) Imaging mass spectrometry: hype or hope? J Am Soc Mass Spectrom 20(6):1006–1014

    Article  CAS  PubMed  Google Scholar 

  • Hsieh Y, Chen J, Korfmacher WA (2007) Mapping pharmaceuticals in tissues using MALDI imaging mass spectrometry. J Pharmacol Toxicol Methods 55(2):193–200

    Article  CAS  PubMed  Google Scholar 

  • Hsieh Y, Li F, Korfmacher WA (2010) Mapping pharmaceuticals in rat brain sections using MALDI imaging mass spectrometry. Methods Mol Biol 656:147–158

    Article  CAS  PubMed  Google Scholar 

  • Izmer A, Gholap D, De Houwer K, Cuyckens F, Vanhaecke F (2012) A pilot study on the use of laser ablation-ICP-mass spectrometry for assessing/mapping the distribution of a drug and its metabolites across the body compartments of rats. J Anal At Spectrom 27(3):413–418

    Article  CAS  Google Scholar 

  • Jones EA, Lockyer NP, Vickerman JC (2007) Mass spectral analysis and imaging of tissue by ToF-SIMS—the role of buckminsterfullerene, C60 +, primary ions. Int J Mass Spectrom 260(2–3):146–157

    Article  CAS  Google Scholar 

  • Kempson IM, Martin AL, Denman JA, French PW, Prestidge CA, Barnes TJ (2010) Detecting the presence of denatured human serum albumin in an adsorbed protein monolayer using. TOF-SIMS Langmuir 26(14):12075–12080

    Article  CAS  PubMed  Google Scholar 

  • Kempson IM, Chang P, Bremmell K, Prestidge CA (2013) Low temperature thermal dependent Filgrastim adsorption behavior detected with ToF-SIMS. Langmuir 29(50):15573–15578

    Article  CAS  PubMed  Google Scholar 

  • Khatib-Shahidi S, Andersson M, Herman JL, Gillespie TA, Caprioli RM (2006) Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry. Anal Chem 78(18):6448–6456

    Article  CAS  PubMed  Google Scholar 

  • Klinkert I, Chughtai K, Ellis SR, Heeren RMA (2014) Methods for full resolution data exploration and visualization for large 2D and 3D mass spectrometry imaging datasets. Int J Mass Spectrom 362(1):40–47

    Article  CAS  Google Scholar 

  • Lanzarotta A, Crowe JB, Witkowski M, Gamble BM (2012) A multidisciplinary approach for the analysis of an adulterated dietary supplement where the active pharmaceutical ingredient was embedded in the capsule shell. J Pharm Biomed Anal 67–68:22–27

    Article  PubMed  Google Scholar 

  • Lee TG, Park JW, Shon HK, Moon DW, Choi WW, Li K, Chung JH (2008) Biochemical imaging of tissues by SIMS for biomedical applications. Appl Surf Sci 255(4):1241–1248

    Article  CAS  Google Scholar 

  • Liu X, Qu S, Lu X, Ge X, Leng Y (2009) Time-of-flight secondary ion mass spectrometry study on the distribution of alendronate sodium in drug-loaded ultra-high molecular weight polyethylene. Biomed Mater 4(6):065008

    Article  PubMed  Google Scholar 

  • Liu X, Ide JL, Norton I, Marchionni MA, Ebling MC, Wang LY, Davis E, Sauvageot CM, Kesari S, Kellersberger KA, Easterling ML, Santagata S, Stuart DD, Alberta J, Agar JN, Stiles CD, Agar NY (2013) Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging. Sci Rep 3:2859

    PubMed  PubMed Central  Google Scholar 

  • Nyadong L, Harris GA, Balayssac S, Galhena AS, Malet-Martino M, Martino R, Parry RM, Wang MD, Fernández FM, Gilard V (2009) Combining two-dimensional diffusion-ordered nuclear magnetic resonance spectroscopy, imaging desorption electrospray ionization mass spectrometry, and direct analysis in real-time mass spectrometry for the integral investigation of counterfeit pharmaceuticals. Anal Chem 81(12):4803–4812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oetjen J, Aichler M, Trede D, Strehlow J, Berger J, Heldmann S, Becker M, Gottschalk M, Kobarg JH, Wirtz S, Schiffler S, Thiele H, Walch A, Maass P, Alexandrov T (2013) MRI-compatible pipeline for three-dimensional MALDI imaging mass spectrometry using PAXgene fixation. J Proteom 90:52–60

    Article  CAS  Google Scholar 

  • Pajander J, Haugshøj KB, Bjørneboe K, Wahlberg P, Rantanen J (2013) Foreign matter identification from solid dosage forms. J Pharm Biomed Anal 80:116–125

    Article  CAS  PubMed  Google Scholar 

  • Parson WB, Koeniger SL, Johnson RW, Erickson J, Tian Y, Stedman C, Schwartz A, Tarcsa E, Cole R, Van Berkel GJ (2012) Analysis of chloroquine and metabolites directly from whole-body animal tissue sections by liquid extraction surface analysis (LESA) and tandem mass spectrometry. J Mass Spectrom 47(11):1420–1428

    Article  CAS  PubMed  Google Scholar 

  • Physical Electronics, Inc., USA (2010) TOF-SIMS imaging of a drug pellet cross-section using a Bi3 2+ cluster ion beam

    Google Scholar 

  • Reyzer ML, Caldwell RL, Dugger TC, Forbes JT, Ritter CA, Guix M, Arteaga CL, Caprioli RM (2004) Early changes in protein expression detected by mass spectrometry predict tumor response to molecular therapeutics. Cancer Res 64(24):9093–9100

    Article  CAS  PubMed  Google Scholar 

  • Rohner TC, Staab D, Stoeckli M (2005) MALDI mass spectrometric imaging of biological tissue sections. Mech Ageing Dev 126(1):177–185

    Article  CAS  PubMed  Google Scholar 

  • Schadt S, Kallbach S, Almeida R, Sandel J (2012) Investigation of figopitant and its metabolites in rat tissue by combining whole-body autoradiography with liquid extraction surface analysis mass spectrometry. Drug Metab Disposition 40(3):419–425

    Article  CAS  Google Scholar 

  • Schwamborn K, Caprioli RM (2010) Molecular imaging by mass spectrometry-looking beyond classical histology. Nat Rev Cancer 10(9):639–646

    Article  CAS  PubMed  Google Scholar 

  • Scoutaris N, Hook AL, Gellert PR, Roberts CJ, Alexander MR, Scurr DJ (2012) ToF-SIMS analysis of chemical heterogeneities in inkjet micro-array printed drug/polymer formulations. J Mater Sci Mater Med 23(2):385–391

    Article  CAS  PubMed  Google Scholar 

  • Shur J, Price R (2012) Advanced microscopy techniques to assess solid-state properties of inhalation medicines. Adv Drug Del Rev 64(4):369–382

    Article  CAS  Google Scholar 

  • Soltwisch J, Göritz G, Jungmann JH, Kiss A, Smith DF, Ellis SR, Heeren RMA (2014) MALDI mass spectrometry imaging in microscope mode with infrared lasers: bypassing the diffraction limits. Anal Chem 86(1):321–325

    Article  CAS  PubMed  Google Scholar 

  • Takai N, Tanaka Y, Inazawa K, Saji H (2012) Quantitative analysis of pharmaceutical drug distribution in multiple organs by imaging mass spectrometry. Rapid Commun Mass Spectrom 26(13):1549–1556

    Article  CAS  PubMed  Google Scholar 

  • Wendeln C, Heile A, Arlinghaus HF, Ravoo BJ (2010) Carbohydrate microarrays by microcontact printing. Langmuir 26(7):4933–4940

    Article  CAS  PubMed  Google Scholar 

  • Zhou Q, Qu L, Gengenbach T, Denman JA, Larson I, Stewart PJ, Morton DAV (2011) Investigation of the extent of surface coating via mechanofusion with varying additive levels and the influences on bulk powder flow properties. Int J Pharm 413(1–2):36–43

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Future Industries Institute, University of South Australia, Mawson Lakes, SA, 5095, Australia

    Ivan M. Kempson

  2. School of Pharmacy and Medical Sciences, University of South Australia, City East Campus, Adelaide, SA, 5001, Australia

    Clive A. Prestidge

Authors
  1. Ivan M. Kempson
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  2. Clive A. Prestidge
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Corresponding authors

Correspondence to Ivan M. Kempson or Clive A. Prestidge .

Editor information

Editors and Affiliations

  1. Bioneer: FARMA Department of Pharmacy, University of Copenhagen, Copenhagen Ø, Denmark

    Anette Müllertz

  2. Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, Seychelles

    Yvonne Perrie

  3. Department of Pharmacy, University of Copenhagen, Copenhagen Ø, Denmark

    Thomas Rades

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© 2016 Controlled Release Society

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Kempson, I.M., Prestidge, C.A. (2016). Mass Spectrometry Imaging of Pharmaceuticals: From Tablets to Tissues. In: Müllertz, A., Perrie, Y., Rades, T. (eds) Analytical Techniques in the Pharmaceutical Sciences. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-4029-5_19

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