Impact of LC-MS/MS quantification methods on analytical results by example of nationwide U.S. environmental samples

Although different quantification methods are extensively used in environmental chemistry, the impact of the choice of method on the quality and range of analytical results is understudied. This two-part study consists of (a) in-lab evaluation and (b) a traditional meta-analysis (n = 66) of commonly used quantification methods): (i) external calibration; (ii) isotope dilution method with authentic target analogs; (iii) isotope dilution with non-target standards; and (iv) standard addition prior to LC-MS/MS in liquid chromatography tandem mass spectrometry (LC-MS/MS) by example of antibiotics in sewage sludge from across the U.S. Using method (i) as the benchmark quantification method for the antibiotic erythromycin in biosolids, other quantification methods resulted in an overestimation (110-450 %) or an underestimation (10-60 %). Using the method (iv) as the benchmark for other compounds resulted in an overestimation (101-14,700 %) or an underestimation (6-98 %). Matrix effects were also observed and were dependent on the matrix and analyte type. For example, in the case of erythromycin, all sample matrices showed signal suppression. This study showed that in the absence of isotopically labeled analogs, the most accurate alternate quantification method may need to be experimentally determined depending on the analyte. Analysis of published literature on pharmaceuticals in sewage sludge indicated that isotope dilution with authentic target analog is most commonly used, followed by non-target isotope standards, standard addition, and finally external calibration.