With the Chemical Weapons Convention having gone into effect, laboratories that analyze these agents are increasingly important. Analytical Chemistry profiles two groups that are taking different approaches to chemical warfare agent monitoring.
Analytical compet e n c e and the fight against chemical weapons
These real samples typically came from places of alleged use or production of chemical warfare agents, which have been inspected by United Nations officials. Correctly analyzing real samples is critical because a false-positive result would erroneously accuse a chemical company or even a nation of producing chemical weapons. As a result, numerous round-robin and interlaboratory proficiency tests have been organized for method development purposes and, further, to verify the competence of laboratories seeking designation by die OPCW. To become a designated OPCW facility, a laboratory must score well on proficiency tests, must operate under the guidelines of an adequate quality assurance system, and must be accredited by an internationally recognized accreditation body. To date, there have been about 10 international round robins and proficiency tests. The NC Laboratory passed them all with top rankings and also successfully prepared the samples for the first official OPCW proficiency test. In fact, the Analytical Chemistry and Verification branch fulfilled all the requirements for accreditation in the analysis of samples for the presence of chemical warfare agents and related compounds in 1992 and expects to obtain OPCW designation shortly
By April 29,1997, enough states had ratified the international Chemical Weapons Convention (CWC)—which prohibits the development, production, storage, and deployment of these weapons—that the treaty went into effect. With the convention has come the difficult task of enforcing the previsions—and that is putting significant demands on analytical chemistry. The Organization for the Prohibition o: Chemical Weapons (OPCW), seated in The Hague (The Netherlands), is in charge of the worldwide surveillance of CWC compliance. OPCW, in turn, has been recruiting teams of inspectors and designated laboratories to specialize in the analysis of various samples for the presence of chemical warfare agents and related compounds. One of the leading laboratories in this conplex area is the NC Laboratory in Spiez, The proficiency testing has been a rigSwitzerland (NC stands for Nuclear and orous process. A typical scenario is as folChemical threats and risks). lows: One of the about 25 laboratories participating in the test prepares the samples, The Swiss Federal Military Department such as soil, water, clothing and so on, originally established the NC Laboratory as which are contaminated with an unknown a technical facility for developing ways to number of different chemicals (as well as protect against chemical weapons. As the diesel oil, plasticizers, or other compounds demand for such studies has lessened, part that will confound the of the laboratory has analytical data). The instead become a facility other laboratories must for inspection and verififind and identify all cation. "So far we have relevant chemicals. been busy with the establishment of certified To illustrate how analytical methods for demanding even a the qualitative and quanqualitative analysis titative determination of can be, consider the compounds related to class of nerve agents the CWC with participaencompassing the altion in international kylphosphonofluoriround-robin and profidates (see above). ciency tests and with According to the acthe analysis,of real samtual lists of chemicals ples " says Andreas to be surveyed under Niederhauser head the CWC R can be the six-person Analytical methyl, ethyl, n- or Chemistrv and Verificawo-propyl, and the alFT-IR at work in a chemical weapons tion groun kyl substituent R' can lab.
be anything from C1 to C10, including branched and cyclic isomers. (A well-known compound in this class is Sarin with R = The general structure methyl and R' = of the alkylphosphonoisopropyl.) Befluoridates. cause many other classes of chemical warfare agents, precursors, and degradation products are included in the CWC lists, it is obvious that a huge number of dangerous chemicals could exist that are neither commercially available nor have been synthesized. In the Spiez NC Laboratory the samples are analyzed simultaneously by various approaches because at least two different, preferably spectroscopic, methods will be necessary for positive identification. However, it is not known in advance which are successful. Sample preparation is rather specific and depends on the type of matrix. Various couplings of chromatography with spectroscopy or special detectors are used: GC/MS (different ionization techniques), GC/FT-IR GC/atomic emission detector (which gives a fast identification of heteroatoms present in a certain compound), GC/flame photometric detector, LC/MS (different ionization techniques) or CE/ MS If enough sample is available the structure can be identified by NMR Usually the confirmation is done by compounds synthesized in the organic chemistry branch of the NC Laboratory which maintains a large number of precursors in stock and has developed protocols for the rapid preparation of compounds With CWC just getting started, Niederhauser and his team expect numerous opportunities to continue to refine their analytical competence to a high level. Veronika Meyer
Frequent flyer lab Can a fully equipped lab buckle its seat belt and travel to where it's needed most? This means tackling emergency analyses and getting evidence expediently. Flying laboratories are designed to fight terrorism and chemical weaponry by analyzing air, soil, and water on location. Called "Mod-U-Lab" by some and "FlyAway-Lab" by others, these mobile labora-
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News
LABORATORY PROFILE Teenage technique coming of age We are enjoying the formative years of a technique that will soon bloom and grow into a mature analytical tool as commonly used and as powerful as HPLC, according to Tony Moffat. He is a mentor to the impulsive teenager, providing a stable home at the Centre for Pharmaceutical Analysis at the School of Pharmacy, University of London (U.K.). Near-IR (NIR) spectroscopy may soon be the tool of choice for many analytical scientists. The NIR was observed by astronomer William Herschel in 1800 in the Sun's electromagnetic spectrum, but spectroscopists may be more familiar with the mid-IR region, which is widely used to determine chemical structure. The use of the NIR is just beginning to catch up. Moffat is keen to demonstrate that NIR is not a secondary technique. "The great advantage of NIR over other techniques," he explains, "is its applicability to unprepared samples." NIR can analyze liquids and powders alike without pretreatment. "It's as simple as loading the sample, shutting the lid, and pressing the button," Moffat enthuses. "The spectrum appears in 40 s flat—the paperwork afterwards takes the time," he jokes. What kind of information does NIR provide, and why does Europe need a center of excellence for such a seemingly simple technique? NIR is entirely nondestructive and has been used for 30 years by the food and agricultural industries to simultaneously measure protein, carbohydrate, fat, and moisture content in grain and foods. "It is only during the last 15 years, and more particularly the last five teenage years that
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its use in the pharmaceutical industry has been recognized," says Moffat. He believes it will soon come to the fore. Flipping the NIR switch can tell you an awful lot about a pharmaceutical in raw powder form. "NIR can look at physical properties such as particle size, polymorphism and crystallinity, as well as moisture content." Such information is vital in the formulation of a drug. Particle size affects compaction properties in tablet production, whereas crystal type alters solubility properties, which influence drug efficacy and side effects. NIR can also quickly spot a fraudulent, impure, or degraded tablet without even taking it out of the blister pack, simply by comparing the spectrum of a suspect package to a library standard. Moffat believes NIR will become increasingly important in all stages of the manufacturing process—from drug discovery and development to process monitoring and quality control—because it is so easy to carry out. Results are provided online rather than from a remote laboratory analysis. "Our Centre is collaborating with combinatorial chemists and materials scientists interested in surface properties," says Moffat. Combinatorial chemists want to keep track of their multitude of compounds without time-consuming labeling steps, whereas materials scientists are interested in the crystal properties of pharmaceutical products NIR could be the answer for both of them The Centre's role in the life of NIR is to help it through its formative years. Eight strategic industrial partners, including pharmaceutical giants SmithKline Beecham, GlaxoWellcome, and Eli Lilly, provide funding for seven postgraduate students for three years. The students dedicate half their time to company projects and the rest to the Centre's work. Four instrument manufacturers— Bran+Luebbe, Buhler, Anatec, and NIRSystems—have provided the instruments, technical support, experience, and, most importantly, Moffat says, "goodwill". This sharing attitude among the Centre, industry, and manufacturers is helping NIR mature and the Centre with it. "We can now act as an interface between the industry and regulatory authorities," explains Moffat. The Centre helps industry with generic and sometimes spe-
Analytical Chemistry News & Features, January 1, 1998
Centre staff are trying to demystify NIR.
cific problems and at the same time is promoting the solutions to the regulatory authorities. The Centre intends to work with U.K. regulators to provide guidelines for the use of NIR in the pharmaceutical industry that can be proposed to the Committee on Proprietary Medicinal Products (the appropriate European Union authority). It is also assisting in the process of approving NIR for pharmacopoeial use via the EuPharmacopoeia consultation process. "We hope to harmonize the NIR guidelines and to help demystify the black-box image of the technique for industry scientists and regulators alike " he explains The harmonized guidelines will apply equally in Europe the United States and Japan The Centre has spent most of its first year getting its act together but has still found time to publish papers in international journals, present papers at pharmaceutical conferences, and establish academic collaborations with NIR experts in Barcelona, Spain, and Tubingen, Germany. Centre personnel presented a talk at the meeting of the American Association of Pharmaceutical Scientists, in November 1997, in Boston. Moffat says, "I turned down three other invitations to visit [Boston] last year because of other Centre commitments." As if to confirm the spirit of goodwill, the Centre held its first annual meeting last December, giving those involved a chance to catch up and discuss problems. Most importantly though, felt Moffat, such meetings give him and his colleagues at the Centre—Roger Jee and Robert Watt—the chance to talk with their industrial and regulatory contacts in the bar afterwards! Perhaps NIR really is coming of age. David Bradley
tories were originally designed to serve the multilateral Chemical Weapons Agreement and the Wyoming Memorandum of Understanding. These jet-setting labs have traveled around the world, making stops in Switzerland, the United Kingdom, Iraq, and the United States—most notably serving at the Summer Olympics in Atlanta and the Democratic National Convention. According to Monica Heyl, program manager for the Army Material Command Treaty Laboratory, "The lab not only needs to land where it's supposed to be, but also must be fully operational and self-sustainable." The U.S. Army's Chemical and Biological Defense Command at the Aberdeen Proving Ground has relied on Heyl's assistance to develop a flying lab capable of producing results on the spot Heyl enlisted ENG Mobile Systems, Hewlett-Packard, and EAI Corporation to make it happen. The data from the instrumentation had to be accurate in order to withstand safety and regulatory challenges—not to mention the intricacies of politics in various destinations. The Chemical Weapons Convention prohibits the production, use, and storage of chemical weapons. Inspectors cannot remove any samples from the country, which minimizes the potential for claiming that samples were tampered with offsite. Precursors and degradation products in air, soil, and water samples require analyses in the areas in which they are found to comply with current laws. "Detectors, methods, and field operating principles were designed, demonstrated, and evaluated to test field efficacy," says Heyl. "Proper collection of samples, elimination of cross-contamination, and
assurance of chain of custody are difficult to prove unless you are willing to prepare the samples in the field. Each day we deal with significant mandates to provide accurate and defensible reports," says Heyl. Airline regulations of weight and size also needed to be considered-^along with bundling the right instrumentation. Dick Glass of ENG, along with Tom Albro, Patti Riggs, and Rodney Hudson of EAI Corporation handled the logistics. "Pulling together mobile systems that comply with the needs of the mission and are easy for a couple of people to move is a must. About 150 lbs is what two individuals can carry. We created modules of a total analytical system that met the limits. However, try as we did to meet such standards a couple of heavier systems still require more manpower to unload safely" Glass admits. Albro states, "EAI had to use off--he-shelf analytical equipment and get it into rugged packaging." Heyl takes it a step further. "You need to think about power, compressed gases, a viable operational environment, size and weight, and the ergonomics for efficient transport and integration." Laptop computers run the instrumentation. One controls the gas chromatograph, which is equipped with both a dualwavelength flame photometric detector and a quadrupole mass-selective detector. Optional detectors include a pulsed-flame photometric detector, a halogen selective detector, and thermal conductivity detector. Other available instrumentation includes an FT-IR spectrometer, an ion chromatograph, and a high-performance liquid chromatograph. Included also are the tools for obtaining samples and preparing them correctly. Gray Gil-
fillan, a Joint Services Group team leader at Hewlett Packard, was responsible for integrating the system hardware and software for this array of equipment. To be effective at once, the Fly-AwayLab demands self-supporting capabilities, both to protect the safety of the team and the efficacy of the analyses. On-board generators prevent power fluctuations that can devastate data collection and shut down the instrument. "Because the lab must verify a variety of compounds at the ppm or lower levels, transporting the equipment and not being vulnerable to susceptibility, such as cheating, spoofing, and circumventing, is imperative," says Albro. Active and reliable upon arrival, the FlyAway-Lab was designed to use minimal amounts of hazardous materials or nonvital components for more than simple convenience. "Imagine going through customs, unloading equipment, calibrating everything, and conducting analyses within hours," says Heyl. The laboratory has been streamlined since its original inception. Lighter cases, hoods with filtration, thermal desorption units for automated analyses of air samples, and a supertoxic glove-box system to take care of high-concentration warfare agents have been added. Future plans include looking at miniaturized LC/MS and CE systems to ensure additional strength in chemical, biological, and radiation analyses capabilities. The lab's globetrotting days are far from over. "The Fly-Away-Lab is earning more frequent-flyer miles than most of my colleagues put together," says Heyl. Crispin Littlehales
tors for the environmental (IAETL) section, and that is new. There has not been a board of directors for individual sections [of ACIL] prior to this," says Janis Butler of Continental Analytical Services and cochair on the IAETL section board. "We will have our own director who will report to the IAETL section board on policy issues and to the ACIL executive director on administrative issues." The new IAETL section board is composed of roughly one-half former IAETL members and one-half ACIL members S3.VS Butler. IAETL was formed in 1988 to address issues such as certification/accreditation
and tax-favored competition, faced by the environmental testing industry in the United States and Canada. ACIL, founded in 1937, is a broader-based association representing independent, commercial scientific and engineering laboratories, as well as testtng, ,onsulting, and R&D firms. The two ooganizations have long been in competition, which, according to some, resulted in an unnecessary duplication of efforts. 'We were too small an organization to have an effective voice in Washington," says Ron Hass, president and CEO of Triangle Labs. The environmental testing industry has undergone significant consolidation over
GOVERNMENT
IAETL becomes the environmental section of ACIL On Jan. 1, the International Association of Environmental Testing Laboratories (IAETL) merged with the national trade organization ACIL. Many believe that this will provide a stronger, more unified voice in Washington for environmental testing laboratories. The environmental section of ACIL will now be referred to as the IAETL section and will operate semiautonomously within ACIL. "There will be a separate board of direc-
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