Inside Instrumentation

PUBLIC CONCERN about what exactly is in our water is motivating authorities to go beyond their routine testing. Fueling these concerns are news reports suggesting that pharmaceuticals, in particular, are already in 24 city water supplies. The World Health Organization, Environmental Protection Agency, and others are now investigating the issue.

"For government to react and make informed decisions on risk assessment, it needs scientific information based on analytical methodologies," says Joe Romano, senior manager in the chemical analysis market development group at Waters Corp., in Milford, Mass.

Seeing an apparent gap in the ability of public water authorities to respond, Waters offered a complimentary program earlier this year to test drinking water for pharmaceuticals. Although the results are confidential, Romano calls it a success on the basis of the response and amount of baseline data it collected.

At the same time, technology itself is driving interest in screening for pharmaceutical contaminants. As sample preparation and instrumentation have improved, Romano points out, "we can detect things that we couldn't see 10 years or even a year ago." With available technologies, one can monitor nanogram-per-liter, or part-per-trillion, drug contaminant levels in drinking water or wastewater, says E. Michael Thurman, who in April helped set up the Center for Environmental Mass Spectrometry (CEMS) at the University of Colorado, Boulder.

Work at CEMS will focus on detecting and treating pharmaceuticals in water. "There's a long list of things yet to be understood," Thurman remarks. Collaborators include professor Karl Linden, who helped establish the lab; Agilent Technologies scientists, and others at U.S. Geological Survey labs nearby.

Beyond seeing new analytes, lower detection limits also allow researchers to study transformation processes, writes EPA chemist Susan D. Richardson in her biennial reviews of analytical developments (Anal. Chem. 2008, 80, 4373, and 2007, 79, 4295). Such processes can lead to metabolites or degradants that may be more hazardous than the original parent compounds.

To detect pharmaceuticals, tandem MS with multiple reaction monitoring has become commonplace as sensitivity and selectivity have improved, she says. Gas chromatography can be combined with MS, but calls for derivatization of analytes. High-performance liquid chromatography (HPLC) avoids this step and is widely used for water-soluble compounds.

Nevertheless, screening for multiple analytes in complex environmental samples is challenging. Instrumentation companies have developed MS systems and methods for detecting drug compounds in water. One aim is to make analysis more straightforward.

For example, Waters offers the AquaAnalysis system, which integrates automated on-line solid-phase extraction (SPE) for sample preparation with HPLC and its Quattro micro tandem MS. It uses a reduced sample size and can generate results in 30 minutes instead of hours.

PUBLISHED IN DECEMBER 2007, EPA's detailed 77-page analytical method 1694 refers to using Waters' SPE, HPLC, and MS—or equivalent—equipment. The method covers 74 common drugs—largely antibiotics, antidepressants, and over-the-counter painkillers—and personal care compounds in environmental samples.

EPA researchers recently looked at 48 pharmaceuticals and six metabolites they consider ecologically relevant. Their goal was to develop a rapid, sensitive, and accurate method to simultaneously analyze a targeted list of analytes with a broad range of chemical properties.

After extracting the analytes off-line by SPE, the EPA team used Waters' ultraperformance LC-MS/MS system (Anal. Chem. 2008, 80, 5021). Compared with HPLC, UPLC can increase resolution and sensitivity, while reducing analysis time and solvent use, they note.

Agilent scientist Jerry Zweigenbaum, along with Thurman and CEMS research scientist Imma Ferrer, have published an approach to method 1694 using an Agilent 6410A triple quadrupole LC/MS. The company also has equipped the university's new center with an Agilent Accurate Mass 6220 time-of-flight LC/MS.

Despite all the work that's been done and is under way, only about 150 of the 3,000 different substances used as pharmaceutical ingredients have been investigated in environmental studies, according to Richardson. And new analytical methods and instruments are pushing detection limits to picogram-per-liter levels.

Ultimately, though, what's important is not just how to look, but coming up with a list of what to look for. Even as they develop better analytical technologies and methods, Thurman and others say that it's not clear exactly what drug-related compounds should be targeted for detection and removal.

"Just because you detect something, is it meaningful?" Thurman asks. Questions regarding the amount and long-term effects of drug contaminants still need to be answered (see page 36).