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Clean Water Act Analytical Methods

Method 1694 - Frequent Questions

EPA Method 1694 covers 73 pharmaceuticals and personal care products (PPCPs). The method was developed at Axys Analytical Services, Ltd. We have answered questions about use of this method in general, and for specific situations.

Why was EPA Method 1694 developed?
To screen wastewater treatment plant (WWTP) matrices- - influent, effluent and biosolids -- for a wide range of pharmaceuticals and personal care products.
Is Method 1694 a regulatory, i.e. a Part 136, method?
No. It has been validated in a single lab, peer-reviewed, and used to screen samples from various sources to profile occurrence of PPCPs.
Is it necessary to analyze for all the chemicals in Method 1694?
No. When screening complex matrices, such as WWTP wastewaters and solids, monitoring for a subset of 15- 20 chemicals may produce better results, if cleanup procedures are tailored for those chemicals in your matrix, and especially if the subset pairs a target chemical with an isotopic analog. The 73 chemicals in Method 1694 include several classes of chemicals from which one or two chemicals representative of each class could be selected, and several of which have commercially available isotopes.
Besides including a chemical from each PPCP class of interest, how might I select a subset of 15 – 20 target PPCPs?
Project specific considerations might include the availability of ecological or toxicity information, an evaluation of existing occurrence data, availability of labeled isotopes, and regulatory barriers, such as Drug Enforcement Administration (DEA) licensing.
May I alter the extraction and clean up techniques in Method 1694?
Yes, modifications that improve the accuracy and precision associated with individual subsets of compounds or individual matrices are encouraged. The modifications should be documented and provide performance equal or better than that specified in the method.
Why does Method 1694 not include an isotope for each of the 73 target chemicals?
The isotope dilution techniques used in EPA Methods, such as 1624, 1625, and 1668, improve the accuracy of measurements of individual chemicals in challenging matrices, such as WWTP wastes. However, not all PPCPs have commercially available labeled analogs. The cost of synthesizing small amounts of custom-made isotopes is very expensive. For Method 1694, we used less expensive, commercially available isotopes that are made for a larger market.
May additional chromatography columns be used with EPA Method 1694?
Yes, but note that the method has a specific minimum retention time requirement for each specified column. The use of minimum retention times helps to control false positives. Thus if you use a different column, to maintain the selectivity of the LC/MS/MS technology, establish minimum retention times for your column, and monitor for secondary MRM transitions.
Why not use less expensive and more widely available Gas Chromatography (GC) Low Resolution Mass Spectrometry to measure the PPCPs?
Polar and/or thermally unstable analytes such as pharmaceuticals may only be amenable to GC when derivatized, which adds another source of variability to the measurement. We chose LC because it is ideal for less volatile, thermally unstable and/or polar compounds, and LC does not require derivatization of the target PPCP.
What changes should not be made to Method 1694?
Changes to the determinative step (e.g., the detector), or the quality control requirements.
Is Method 1694 a useful template for developing a custom PPCP method?
Yes, the information in 1694 or similar LC/MS/MS methods may be used as a starting point to develop an analytical method tailored to specific matrices or compounds.
Besides adapting Method 1694 to my needs, what other methods might be suitable for analysis of PPCPs in WWTP wastewaters?
There are less standardized analytical methods in journal articles, and on some websites. These methods often require additional development before use, such as establishing holding times, data acceptance criteria, and quality control checks. When evaluating the suitability of a candidate method for your application look for: detailed extraction and cleanup protocols, retention times, instrumental parameters, such as collision energy, MRM transitions (preferably primary and secondary), detection limits, and performance data documenting acceptable performance in your matrix. Peer review of the method is also a useful feature. The following article is an example of suitable information:
Angela L. Batt, Mitch S. Kostich, and James M. Lazorchak. "Analysis of Ecologically Relevant Pharmaceuticals in Wastewater and Surface Water Using Selective Solid-Phase Extraction and UPLC−MS/MS." Anal. Chem. 2008, 80, 5021– 5030. DOI: 10.1021/ac800066n Exit