ICP-MS

1. INDUCTIVELY COUPLED PLASMA MASS SPECTROMETER (ICP-MS) 29-09-2012

2. OVERVIEW INTRODUCTION INSTRUMENTATION PRINCIPLE Sample introduction Ion source Mass analysers Detection unit Peak measurement Methods of quantitation Interferences PHARMACEUTICAL APPLICATIONS NEXT GENERATION OF ICP-MS CONCLUSIONS

3. INTRODUCTION What is ICP-MS ? I nductively C oupled P lasma M ass S pectrometry Elemental analysis with: Wide elemental coverage Very low detection limits( ppt /ppm) Fast analysis times (all elements at once) Simple spectra Isotopic information

4. LIMITS OF DETECTION : IN COMPARISION

5. Why is ICP-MS unique? ICP-MS can : measure almost any element at ppt to ppm levels in almost any material. measure all elements in a single analysis. distinguish different element species (speciation ). Main requirements in pharmaceutical analysis are : high sensitivity good matrix tolerance low levels of interferences ease of coupling to speciation techniques ( LA, LC and maybe GC)  

6. INSTRUMENTATION USING PERISTALTIC PUMP(1ml/min) TO SEPARATE FINE DROPLETS (1-2%)FROM LARGER ONES 2 METALLIC CONES (SAMPLER AND SKIMMER CONE ( 0.6-1.2mm ORIFICE, AT 760 TORR) 750-1500W

7. PRINCIPLE Liquid samples to form aerosol in nebulizer. Introduction of Argon to the ICP torch, which is located in center of a radio frequency (RF) coil for energy supply. RF field causes collisions of Ar atoms, generating a high-energy plasma. Sample aerosol decomposed in plasma (6000 - 10000 K) to form analyte atoms which are simultaneously ionized. Ions extracted from the plasma into mass spectrometer region.

8. SAMPLE INTRODUCTION

9. SAMPLE INTRODUCTION DATA ANALYSIS

10. 1.QUADRUPOLE MASS SPECTROMETER dc field on one pair of opposite rods and RF field on the other pair. Ions of a selected m/z ratio are allowed to pass through the rods of the detector. MASS ANALYSERS

11. 2.MAGNETIC SECTOR FIELD

12. 3.DOBLE FOCUSSING SECTOR MS ESA- kinetic energy focusing Magnet : ions travel in a curved path and are separated according to their m/z.

13. 1.SECONDARY ELECTRON MULTIPLIER Incoming ion creates an electron. Acceleration of electron towards the second dynode. Electron cascade is analysed as pulse or current. DETECTION UNIT

14. 2.FARADAY CUP Incoming ion draw an electron from the ground to neutralize the positive charge of the incoming ion. A voltage is measured.

15. 3.MULTIPLE COLLECTOR DEVICES Multiple detectors are aligned parallel. Nuclides are measured simultaneously. Prerequisite for precise isotopic ratio measurement.

16. MULTI COLLECTOR ICP-MS

17. PEAK MEASUREMENT MEASUREMENT VARIABLES: Whether it is a continuous or transient signal . The temporal length of the sampling event. Volume of sample available. Number of samples being analyzed. Number of replicates per sample. Number of elements being determined. Detection limits required. Precision/accuracy expected. Dynamic range needed. Integration time used.

18. METHODS OF QUANTITATION Quantitative analysis Semiquantitative routine Isotope dilution Isotope ratio Internal standardization

19. INTERFERENCES Polyatomic Interferences Minimized by: O ptimization of nebulizer gas flow (1.5-1.8ml/min). RF power adjustment (500-800W). 3. Sampling position within plasma. Isobaric Interferences Minimized by : 1. cold plasma technique 2. collision/reaction cell 3. High resolution mass analysers as double focussing magnetic field sector. Matrix Interferences Minimized by: use internal standardization

20. ICP-MS : FIELDS OF APPLICATIONS

21. FIELDS OF APPLICATIONS Qualitative and Quantitative (simultaneous multi element analysis). Isotope ratio measurement Coupling techniques: Chromatographic system Laser ablation

22. LC-ICP-MS Advantages of HPLC Wide applicability High resolution Rapid analysis High sensitivity High reproducibility Quantitative Easily automated ICP-MS as detector Selective for the element Provide isotopic information Determination of multiple elements simultaneously Universal , regardless the mode of chromatography Extremely sensitive Detection limits in ppt range

23. ABLATION ICP-MS Analysis of solid sample surfaces Procedure: • Laser beam focused onto sample surface in ablation chamber or cell. • Miniature plasma above sample ablates material from surface. • Resultant particulate material is transported to ICP-MS with carrier gas stream (e.g. Ar ) • Sample is decomposed, atomised and ionized in ICP plasma and analyzed in mass spectrometer. Applications for LA-ICP-MS: • Monitor distribution of administered drugs among different tissues and body compartments. • In-situ analysis of metals and other elements in samples separated using PAGE, e.g.: – Au and Pt drug metabolite identification. – Determine degree of phosphorylation of different separated proteins.

24. PHARMACEUTICAL APPLICATIONS Pharmaceutical waste water Drug discovery / drug development : Analysis of individual forms of drug compounds using target element analysis Simple metal analysis during development of metal-based drugs QA/QC and process development: National Pharmacopeia (e.g. USP, EP, JP) Testing Impurity limit tests Metals in active pharmaceutical ingredients (API) QC of natural products – toxic impurities Toxic element impurities (e.g. heavy metals ) Clinical trials: Simple metal analysis for active component confirmation Monitoring of the metabolites of an administered drug    

25. Metal impurities – Leachables from pharmaceutical packaging materials 1. Interaction between formulation and packaging material results in components migrating into the drug product. 2. These components may be toxic or affect the stability of the drug product 3. Storage conditions impact leaching (heat, UV radiation, storage time ) Typical leachables are: Small organic molecules [monomers, excipients, reaction by-products], Metal ions and trace elements (e.g. aluminum, cadmium, chromium, copper, lead, manganese , and zinc) Metal ions can affect the stability of the formulation, catalyze the degradation of the active pharmaceutical ingredient (API) and cause unqualified degrades to form , or pose a toxicity threat on their own .

26. NEXT GENERATION OF ICP-MS ( NexION 300 ICP-MS Instruments) Engineered to deliver a level of stability, flexibility and performance never before seen in an ICP-MS instrument, PerkinElmer's NexION ® 300 is the first truly significant and revolutionary industry advancement in recent years .

27. The NexION 300  offers: 3 modes of operation (Standard, Collision and Reaction) and can be quickly switched from 1 mode to another. So , every analysis can be performed on the same instrument . It's the only ICP-MS that lets you maximize productivity without compromising sensitivity or performance. A single ICP-MS instrument offers both the simplicity and convenience of a collision cell and the exceptional detection limits of a true reaction cell. Stability is optimized by incorporating a unique Triple Cone Interface and Quadrupole Ion Deflector. Designed to remove an unprecedented level of un-ionized material (and preventing it from entering the Universal Cell), this innovative ion path keeps the instrument clean, minimizing drift and eliminating the need for cell cleanings.

28. F eatures/Benefits Large, accessible sample introduction system Low liquid uptake nebulizer Free-running RF plasma generator Automated X, Y, Z torch positioning Patented PlasmaLok ® technology Fastest scanning quadrupole in the industry Quadrupole Ion Deflector Triple Cone Interface Plasma View window Four-stage vacuum system Benchtop design

29. APPLICATIONS Gold Nanoparticles Reference Materials Using the NexION 300 ICP-MS in Single Particle Mode. Coupling Flow Field Flow Fractionation to ICP-MS for the Detection and Characterization of Silver Nanoparticles. The Determination of Lead in Calcium-Based Antacid and Dietary Supplements . The Determination of Metals in Cosmetics . Assuring safety of traditional Chinese herbal medicines by monitoring inorganic impurities using ICP-MS.

30. CONCLUSIONS ICP-MS is excellent detector for HPLC in bioanalysis . Orthogonal to other detectors. Rapid and efficient method for metabolism studies /speciation. Polyatomic interferences from high matrix samples are a major challenge. Room for instruments improvements.