[Determination of 145 pharmaceuticals and personal care products in eleven categories in water by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry].

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants frequently detected in aquatic environments at trace levels. These chemicals have diverse structures and physicochemical properties and includes pharmaceuticals like antibiotics, antihypertensive drugs, antiviral drugs, and psychotropic drugs that are widely used in large quantities worldwide. Considering the large number of pharmaceuticals currently in usage, it is crucial to establish a priority list of PPCPs that should be monitored and/or treated first. An accurate understanding of the occurrence and levels of PPCPs in aquatic environments is essential for providing objective materials for monitoring these emerging contaminants. Therefore, accurate, efficient, sensitive, and high-throughput screening techniques need to be established for determining and quantifying PPCPs. This study developed a method for the determination of 145 PPCPs (grouped into eleven categories: antibiotics, antihypertensive drugs, antidiabetic drugs, antiviral drugs, ß-receptor agonists, nitroimidazoles, H2 receptor antagonists, psychotropic drugs, hypolipidemic drugs, non-steroidal anti-inflammatory drugs, and others) in water. The method was based on large volume direct injection without sample enrichment and cleanup and used ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS). Water samples were collected and filtered through a 0.22-µm regenerated cellulose (RC) filter membrane. Subsequently, Na2EDTA was added to the samples to adjust their pH to 6.0-8.0. Internal standards were mixed with the solutions, and because of the addition of Na2EDTA, the interference of metal ions could be eliminated in the determination of compounds, especially for tetracycline and quinolone antibiotics. Among the six filter membranes tested in this study (PES, PFTE-Q, PFTE, MCE, GHP, and RC), RC filter membranes were screened for water sample filtration. The UHPLC-MS/MS parameters were optimized by comparing the results of various mobile phases, as well as by establishing the best instrumental conditions. The 145 PPCPs were separated using an Phenomenex Kinetex C18 column (50 mm×3 mm, 2.6 µm) via gradient elution. The mobile phases were 0.1% (v/v) formic acid aqueous solution containing 5 mmol/L ammonium formate and acetonitrile for positive ion modes, 5 mmol/L aqueous solutions of ammonium formate and acetonitrile for negative ion modes. The samples were quantified using the scheduled multiple reaction monitoring (scheduled-MRM) mode with electrospray ionization in positive and negative ion modes. A standard internal calibration procedure was used to calculate contents of sample. The established method was systematically verified, and it demonstrated a good linear relationship. The average recoveries of the 145 PPCPs at the three spiked levels were in the range of 80.4%-128% with relative standard deviations (RSDs, n=6) of 0.6%-15.6%. The method detection limits (MDLs) ranged from 0.015 to 5.515 ng/L. Finally, the optimization method was applied to analyze the 145 PPCPs in 11 surface water samples and 6 drinking water samples. Overall, 93 (64%) out of the 145 analytes were detected. The total contents of the PPCPs in surface water samples ranged from 276.9 to 2705.7 ng/L. The detection frequencies of antidiabetic, antiviral, and psychotropic drugs were 100%. The total contents of the PPCPs in drinking water samples ranged from 140.5 to 211.5 ng/L, and antibiotics, antidiabetic drugs, and antiviral drugs comprised the largest proportion of analytes (by mass concentration) in drinking water samples. Our method exhibited high analytical speed and high sensitivity. It is thus suitable for the trace analysis and determination of the 145 PPCPs in environmental water and showed improved detection efficiency for PPCPs in water, indicating that it has a high potential for practical applications. This study can extend technical support for further pollution-level analysis of PPCPs in water and provide an objective basis for environmental management.

[Determination of 42 antibiotic residues in seven categories in water using large volume direct injection by ultra high performance liquid chromatography-triple quadrupole mass spectrometry].

Antibiotics are emerging contaminants that have recently attracted attention. They have been detected in natural water and pose health concerns owing to potential antibiotic resistance. Antibiotics are ubiquitous in aquatic environments, with a wide spectrum and trace levels. It is difficult to detect all types of antibiotics with completely different physicochemical properties. Solid phase extraction (SPE) is a common sample preparation procedure. For a fast and high-throughput continuous on-line analysis of these emerging contaminants, a method for the determination of 42 antibiotics (grouped into seven categories: sulfonamides, fluoroquinolones, lincosamides, macrolides, tetracyclines, cephalosporins, and chloramphenicols) in environmental water was developed based on ultra high performance liquid chromatography combined with tandem mass spectrometry (UHPLC-MS/MS) involving large volume direct injection without sample enrichment and cleanup. The collected water samples were filtered through a 0.22-µm filter membrane, their pH levels were adjusted to 6.0-8.0 after adding Na2EDTA, and then the solutions were mixed with an internal standard. The addition of Na2EDTA contributed to the release of tetracyclines and fluoroquinolones from the metal chelate. Improved recoveries were observed for all the compounds when the pH of the aqueous solution was set at 6.0-8.0. The optimized UHPLC conditions were as follows: chromatographic column, Phenomenex Kinetex C18 column (50 mm×30 mm, 2.6 µm); mobile phase, acetonitrile and 0.1% (v/v) formic acid aqueous solution; flow rate, 0.4 mL/min; injection volume, 100 µL. In the UHPLC-MS/MS experiment, chloramphenicol, thiamphenicol, and florfenicol were analyzed in the negative ionization scheduled multiple reaction monitoring mode (scheduled-MRM), while the other 39 antibiotics were analyzed in the positive scheduled-MRM mode. This acquisition method improved the response of each target compound by dividing the time of the analysis test cycle and scanning the ion channels of chromatographic peaks at different time periods. The ionspray voltage was set at 5500 and -4500 V in positive and negative modes, respectively. The source temperature for both ionization modes was set at 500 ℃, which was optimized to improve the sensitivity. Instrumental parameters like collision energy and declustering potential were also optimized. Good linearity was observed for all the tested antibiotics, with a correlation coefficient (r) greater than 0.995. The method detection limits (MDLs) were 0.015-3.561 ng/L. The average recoveries ranged from 80.1% to 125%, while the relative standard deviations (RSDs) were between 0.8% and 12.2%. The method was successfully applied to the determination of 10 source water samples and 5 tap water samples. Twelve antibiotics, viz. sulfachloropyridazine, sulfadiazine, sulfamethazine, sulfamethoxazole, sulfisomidine, clindamycin, lincomycin, roxithromycin, clarithromycin, erythromycin, thiamphenicol, and forfenicol, were detected in the 10 water samples with a detection frequency of 100%. The total antibiotic content in each sample ranged from not detected to 80.3 ng/L. Lincosamides and chloramphenicols were the predominant antibiotics in the water samples, with contents in the ranges of 3.83-13.7 and 4.23-33.6 ng/L, respectively. Therefore, the large volume direct injection method exhibited good performance in terms of MDL and recovery compared to standard methods and those reported previously. Compared with traditional pretreatment methods, the large volume direct injection method is simpler, more rapid, more precise, and more accurate. It is a viable alternative to SPE, and can be used for the determination of the 42 antibiotics at trace levels in cleaner water bodies, such as surface water, groundwater, and tap water.

Liquid chromatography tandem mass spectrometry determination of 34 priority and emerging pollutants in water from the influent and effluent of a drinking water treatment plant.

This study evaluates the applicability of a method based on the direct injection of a large volume of water samples to identify and quantify 34 priority and emerging substances, most of them discussed in Directive 2013/39/EU on priority substances in the field of water policy, and Decision 2018/840/EU (Watch List). The method directly injects 500 µL of filtered water sample and so does not use a pre-concentration step. The method was satisfactorily validated for influent and effluent water from a drinking water treatment plant, at three concentrations (1, 10 and 100 ng L-1) with precision and accuracies in the range 1-17% and 71-122% respectively. Sensitivity was good with detection limits in the range 0.15-10 ng L-1 and complied with EU limits in all cases except for estrone, 17-ß-estradiol and 17-α-ethinylestradiol. For these hormones, an on-line solid phase extraction was developed and evaluated. The methods were applied to the analysis of water collected at the influent and effluent of a drinking water treatment plant and revealed the presence of 18 of the target compounds in the influent water and 8 in the effluent water. This showed that most the compounds had been efficiently removed by the processes of the drinking water treatment plant.

Large Volume Direct Injection Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of Carthamus tinctorius Extract and Notoginseng Total Saponins.

The combination of Carthamus tinctorius extract (CTE) and notoginseng total saponins (NGTS), namely, CNP, presents a synergistic effect on myocardial ischemia protection. Herein, comparative pharmacokinetic studies between CNP and CTE/NGTS were conducted to clarify their synergistic mechanisms. A large volume direct injection ultra-high performance liquid chromatography-tandem mass spectrometry (LVDI-UHPLC-MS/MS) platform was developed for sensitively assaying the multi-component pharmacokinetic and in vitro cocktail assay of cytochrome p450 (CYP450) before and after compatibility of CTE and NGTS. The pharmacokinetic profiles of six predominantly efficacious components of CNP, including hydroxysafflor yellow A (HSYA); ginsenosides Rg1 (GRg1), Re (GRe), Rb1 (GRb1), and Rd (GRd); and notoginsenoside R1 (NGR1), were obtained, and the results disclosed that CNP could increase the exposure levels of HSYA, GRg1, GRe, GRb1, and NGR1 at varying degrees. The in vitro cocktail assay demonstrated that CNP exhibited more potent inhibition on CYP1A2 than CTE and NGTS, and GRg1, GRb1, GRd, quercetin, kaempferol, and 6-hydroxykaempferol were found to be the major inhibitory compounds. The developed pharmacokinetic interaction-based strategy provides a viable orientation for the compatibility investigation of herb medicines.

Direct residue analysis of systemic insecticides and some of their relevant metabolites in wines by liquid chromatography - mass spectrometry.

A direct large volume injection (DI-LVI) high performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the quantitative determination of 16 systemic insecticides and their main plant metabolites. The assays were conducted on commercial red and white wines made from grapes grown in major wine-producing regions nationally and internationally. Using a 1:20 dilution and an injection volume of 800µL, a limit of quantitation (LOQ) of 1µgL-1 for all analytes was achieved. Matrix-matched standards (MM) were used for accurate quantitation. Imidacloprid (IMI) and methoxyfenozide (MET) were the most frequently detected parent insecticides in the wines reaching concentrations of 1-132µgL-1. Two important plant metabolites imidacloprid-olefin (IMI-OLE) and spirotetramat-enol (SPT-EN) were found at higher concentrations. In five samples SPT-EN was detected in the mgL-1 range with a maximum concentration of 16.3mgL-1 measured in a conventional white wine sample. Most "organic" wines contained no detectable or low insecticide residues, except for one sample, which showed the highest IMI (14.7µgL-1) and IMI-OLE (331µgL-1) concentrations. Considering the maximum residue limit (MRL) definition for the different insecticides, three "conventional" wine samples were non-compliant for SPT. This study highlights the importance to determine both parent and metabolite forms of systemic insecticides in the finished product.