Quantification of three beta‐lactam antibiotics in breast milk and human plasma by hydrophilic interaction liquid chromatography/positive‐ion electrospray ionization mass spectrometry

Abstract

The use of cephalosporins during breast feeding raises several issues, including the risk of drug exposure through breast milk for the infant. In this paper, a hydrophilic interaction liquid chromatography/positive ion electrospray mass spectrometric assay (HILIC/ESI-MS) was developed for the quantitation of cefuroxime, cefoxitin, and cefazolin in breast milk and human plasma. The assay was based on the use of small sample size, 25 μL of biological samples, following acetonitrile precipitation of proteins and filtration that enabled injection into the HILIC/ESI-MS system. All analytes and the internal standard, alfuzosin, were separated by using a ZIC®-HILIC analytical column (150.0 × 2.1 mm i.d., particle size 3.5 µm, 200 Å) with isocratic elution. The mobile phase was composed of a 6% 12.5 mM ammonium acetate water solution in acetonitrile and pumped at a flow rate of 0.25 mL min . The assay was linear over a concentration range of 0.2 to 5 µg mL and 0.4 to 20 µg mL for all the analytes in breast milk and in human plasma, respectively. Intermediate precision was found to be less than 4.2% over the tested concentration ranges. A run time of less than 12 min for each sample made it possible to analyze a large number of biological samples per day. The method is the first reported application of HILIC in the analysis of antibiotics in breast milk and human plasma and it can be used to support a wide range of clinical studies. Copyright © 2016 John Wiley & Sons, Ltd.

UPLC–MS/MS method for therapeutic drug monitoring of 10 antibiotics used in intensive care units

“…To be applied in routine analysis, the method(s) used for TDM must be fast, accurate, and cost effective. In recent years, the use of liquid chromatography–tandem mass spectrometry (LC–MS/MS) has become the method of choice . While most of the available methods focus on the simultaneous analysis of ß‐lactams, none included the concurrent analysis of Sulfamethoxazole/Trimethoprim and Linezolid, the levels of which are also significantly affected in critically ill patients and which are increasingly used against ß‐lactam‐resistant bacteria such as methicillin resistant Staphylococcus aureus (MRSA).…”

Simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and keto‐doxapram in plasma using liquid chromatography–tandem mass spectrometry

“…In general, for all analytes, our assay performed better than or comparable to prior reported assays, even in comparison with assays measuring only a single analyte, which makes it easier to achieve good performance on run time, required sample volume and matrix effects (Aranda et al, 1988;Carlier et al, 2012;Clavijo et al, 2011;Fernandez Mdel et al, 2013;Hisada et al, 2013;Kiriazopoulos et al, 2017;LeGatt et al, 1986;Lillico et al, 2016;Mahlke et al, 2014;Nichol et al, 1980;Nosseir et al, 2014;Palleschi et al, 2003;Parker et al, 2016;Robson & Prescott, 1977;Saari et al, 2012;Suzuki et al, 2017). Furthermore, most assays use a different drug as an internal standard, whereas we used a deuterated form of fentanyl, which shows better comparable behavior to the analytes that are measured than using a different drug.…”

“…These combinations mostly concerned multiple drugs from the same drug class, i.e. sufentanil or fentanyl with other analgosedatives by Nosseir et al () and Fernandez Mdel et al (), or cefazolin with beta‐lactams by Carlier et al () and Kirziazopoulos et al (). Our assay concerned four drugs from three different anatomical therapeutic chemical classes: fentanyl and sufentanil as nervous system drugs; cefazolin as an anti‐infective drug; and doxapram as a respiratory drug.…”

“…On the other hand, Suzuki et al needed a 12 min run time and used propranolol as an internal standard, where we needed a 5 min run time and used deuterated fentanyl, and our sample preparation required fewer operational steps. Regarding cefazolin, multiple assays have been reported with comparable performance (Carlier et al, ; Kiriazopoulos et al, ; Lillico et al, ; Parker et al, ). The reported fentanyl assays required larger sample volumes except for Hisada et al (), who needed only 20 μL and reached a lower LLOQ of 0.05 μg L −1 compared with our 0.1 μg L −1 .…”

“…Stability during three cycles of freezing and thawing, and freezer stability studies of the analytes in the matrix are not presented because they were already carried out in previous published papers and do not depend on the analytical method. No relevant effects of freezing and thawing were found for all analytes, together with good stability at −20°C for 4 weeks (Clavijo et al, ; Kiriazopoulos et al, ; Mahlke et al, ; Nosseir et al, ; Palleschi et al, ; Parker et al, ; Saari et al, ; Suzuki et al, ).…”