Mass spectrometry, especially HPLC/MS/MS,  is an important and quite useful technique for the detection, identification, quantitation and analysis of small pharmaceutical molecules, peptides, proteins, and oligonucleotides and their metabolites and degradants.  With our SciEx triple quadrupole instruments with  ElectroSpray and NanoSpray ionization, we can be especially effective in the analysis of small quantities of proteins and protein digests.  We also offer APCI (Atmospheric Pressure Chemical Ionization) as this technique sometimes gives better sensitivity than does ESI, especially for small or non-polar molecules.  In addition to conventional tandem triple quadrupole instruments, we also have a SciEx API-4000 Q Trap, which combines the great sensitivity and quantitative accuracy of the other SciEx triple quads with a Linear Ion Trap (LIT) capability.  This allows for both greater sensitivity and the ability to perform MS3.  This enables better and faster degradant identification and peptide sequencing. 

There are several common modes of obtaining mass spectra. These include: Time-of-flight (TOF), quadrupole, ion trap, magnetic sector, and combinations of these. Ionization techniques commonly used in biotechnology and pharmaceutical analysis for non-volatile samples include Matrix-Assisted Laser Desorption/Ionization (MALDI), Electrospray Ionization (ESI), Atmospheric Pressure Chemical Ionization (APCI) and Fast Atom Bombardment (FAB). Each technique has its own set of advantages and disadvantages.  That is, no one technique will solve all problems.  We will be happy to assist you in the choice of technique most appropriate to your needs.

Tandem quadrupole mass spectrometry (MS/MS) is especially useful for the analysis of pharmaceuticals in biological samples because it allows for a very large improvement in the signal to noise ratio (S/N) by effectively excluding interfering substances from the analysis.  Similarly, the use of both CI (chemical ionization) and EI (electron ionization) can increase specificity and sensitivity.  This is why we are able to quantitate many molecules down to the 10pg/mL level in plasma and solid tissues.  We offer both HPLC/MS/MS and GC/MS/MS.  We have established even smaller LOD and LOQ for certain molecules.

One of our specialties is the analysis of anti-proliferative drugs, including paclitaxel (Taxol), rapamycin, tacrolimus, mycophenolic acid, and doxorubicin in both formulated materials and in clinical biosamples, including solid tissues. 

Proteins, peptides, and oligonucleotides may be analyzed by the use of Electrospray Ionization (ESI) of effluents from a liquid chromatograph or capillary electrophoresis system. This is because it is possible to generate an envelope of multiply charged species whose m/z is within the mass range of the spectrometer (generally up to 3000 amu). Deamidation, iso-aspartate formation, and other post-translational modifications and the polymer sequence can be identified in proteins and peptides with relative ease and excellent mass accuracy (1, 2). Oligonucleotide molecular weight determination and sequence confirmation is performed by very similar means, except that the sample preparation is a bit different and negative ion mode is used (3). Because we use quadrupole MS/MS, we are able to perform parent ion scans, which often improves S/N significantly (5).

Our newest acquisitions is a SciEx 4000Q system.  This affords greater sensitivity for both small and large molecules, and adds to our metabolite characterization capability.  Mercedes will join Maude and Mathilde in our happy LC/MS family.

MALDI-TOF is often useful for the same work as is ESI with a quadrupole mass spectrometer, except that the multiply charged ionization is not used. The differences between the techniques are described more fully in reference (4). Other information can be obtained from the American Society for Mass Spectrometry (ASMS) and from manufacturers of the instrumentation.  MS data libraries can be obtained from the NIST and Palisade Corp. The Journal of Mass Spectrometry is an excellent source of practical information and tutorials.  Our RML home page lists many manufacturers and excellent sources of data and scientific information.

There now are several instrument manufacturers who sell combination quadrupole - TOF mass spectrometers for use with HPLC.  They can be enormously useful in some cases, but tend to make conventional triple quadrupoles seem to be inexpensive.

RML also provides drug stress testing (drug degradation) and method development.

On our home page, we list many sources of information regarding proteomics, protein analysis, and mass spectrometry.  Our ANALYTE  page gives a list of some of the compounds for which we have valid analyses.  


1. D. R. Marshak (ed.) "Techniques in Protein Chemistry" This is a series of excellent books which contain papers presented at the Protein Society Symposia. Published by Academic Press. Very inexpensive, remarkably so for the high quality of information provided. The earlier volumes have information which is especially useful to anyone just starting in modern protein and peptide analysis.  See  volumes V and VI, particularly.  (800)-782-4479

2. D. W. Aswad  "Deamidation and Isoaspartate Formation in Peptides and Proteins" CRC Press (1995).

3. J. Stults and J. Marsters "Improved Electrospray Ionization of Synthetic Oligonucleotides" Rapid Comm. in Mass Spec. 5, 359-363 (1991).

4. G. Suizdak "Mass Spectrometry for Biotechnology" Academic Press (1996). This is an excellent introduction to mass spectrometry, in general, and to the biotechnology applications, in particular, and is quite inexpensive. 800-782-4479.

5. G. Neubauer and M. Mann "Parent Ion Scans of Large Molecules" J. Mass Spectrometry 32 94-98 (1997).

6. R. K. Lantz and P. L. Sulik, "Liquid Chromatography - Mass Spectrometry:  A Users Perspective"  European Pharmaceutical Contractor, October, 1998.

7.  R. B. Cole, ed. "Electrospray Ionization Mass Spectrometry:  Fundamentals, Instrumentation, and Applications"  Wiley (1997).  Superb text for both the novice and the expert.

For additional information:

970-266-8108        303-530-1169

Rocky Mountain Instrumental Laboratories, Inc.

108 Coronado Ct.

Ft. Collins, CO 80525