Importance of MS selectivity and chromatographic separation in LC-MS/MS-based methods when investigating pharmaceutical metabolites in water. Dipyrone as a case of study.

Pharmaceuticals are emerging contaminants of increasing concern because of their presence in the aquatic environment and potential to reach drinking-water sources. After human and/or veterinary consumption, pharmaceuticals can be excreted in unchanged form, as the parent compound, and/or as free or conjugated metabolites. Determination of most pharmaceuticals and metabolites in the environment is commonly made by liquid chromatography (LC) coupled to mass spectrometry (MS). LC coupled to tandem MS is the technique of choice nowadays in this field. The acquisition of two selected reaction monitoring (SRM) transitions together with the retention time is the most widely accepted criterion for a safe quantification and confirmation assay. However, scarce attention is normally paid to the selectivity of the selected transitions as well as to the chromatographic separation. In this work, the importance of full spectrum acquisition high-resolution MS data using a hybrid quadrupole time-of-flight analyser and/or a suitable chromatographic separation (to reduce the possibility of co-eluting interferences) is highlighted when investigating pharmaceutical metabolites that share common fragment ions. For this purpose, the analytical challenge associated to the determination of metabolites of the widely used analgesic dipyrone (also known as metamizol) in urban wastewater is discussed. Examples are given on the possibilities of reporting false positives of dypirone metabolites by LC-MS/MS under SRM mode due to a wrong assignment of identity of the compounds detected

Occurrence and removal of pharmaceuticals in wastewater treatment plants at the Spanish Mediterranean area of Valencia

A survey on the presence of pharmaceuticals in urban wastewater of a Spanish Mediterranean area (Castellon province) was carried out. The scope of the study included a wide variety of pharmaceuticals belonging to different therapeutical classes. For this purpose, 112 samples, including influent and effluent wastewater, from different conventional wastewater treatment plants were collected. Two monitoring programmes were carried out along several seasons. The first was in June 2008 and January 2009, and the second in April and October 2009. During the first monitoring, the occurrence of 20 analytes in 84 urban wastewater samples (influent and effluent) was studied. The selection of these pharmaceuticals was mainly based on consumption. From these, 17 compounds were detected in the samples, with analgesics and anti-inflammatories, cholesterol lowering statin drugs and lipid regulators being the most frequently detected groups. 4-Aminoantipyrine, bezafibrate, diclofenac, gemfibrozil, ketoprofen, naproxen and venlafaxine were the compounds most frequently found. In the highlight of these results, the number of analytes was increased up to around 50. A lot of antibiotic compounds were added to the target list as they were considered “priority pharmaceuticals” due to their more potential hazardous effects in the aquatic environment. Data obtained during the second monitoring programme (spring and autumn) corroborated the results from the first one (summer and winter). Analgesics and anti-inflammatories, lipid regulators together with quinolone and macrolide antibiotics were the most abundant pharmaceuticals. Similar median concentrations were found over the year and seasonal variation was not clearly observed. The removal efficiency of pharmaceuticals in the wastewater treatment plants was roughly evaluated. Our results indicated that elimination of most of the selected compounds occurred during the treatment process of influent wastewater, although it was incomplete

Multi-class determination of personal care products and pharmaceuticals in environmental and wastewater samples by ultra-high performance liquid-chromatography-tandem mass spectrometry

In this work, a multi-class method for the simultaneous determination of 17 emerging contaminants, including pharmaceuticals and personal care products, has been developed. Target analytes were two anti-inflammatories, a lipid regulator agent, two angiotensin II antagonists, two antiepileptic drugs and a diuretic. Among personal care products, four preservatives and five UV filters were included. The method is based on solid-phase extraction (SPE) using Oasis HLB cartridges followed by ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Up to three simultaneous transitions per compound were acquired to assure a reliable identification. A detailed study of the extraction process efficiency and matrix effects was carried out in surface water and effluent wastewater. The use of isotope-labeled internal standards (ILIS) was tested to compensate both potential SPE losses during sample extraction and signal suppression/enhancement observed, especially in EWW. Satisfactory correction in all water samples was only ensured when the own analyte ILIS was used. The use of analogues ILIS was a rather useful approach for correction in the majority of the samples tested when analyte ILIS was unavailable. The method was successfully validated in five different surface water (SW) samples and five effluent wastewater (EWW) samples spiked at two concentration levels (0.05 and 0.5 μg/L in SW; 0.1 and 0.5 μg/L in EWW). The developed method was applied to the analysis of 22 samples (SW and EWW) from the Spanish Mediterranean area and 51 reservoir water samples from Colombia. Personal care products were frequently detected, with the highest concentrations corresponding to benzophenone and benzophenone-4 (samples from Spain), and methylparaben (samples from Colombia). Several pharmaceuticals were detected in the Spanish samples, where irbesartan and valsartan – two Angiotensin II antagonists that are not commonly monitored in the aquatic environment – were the compounds most frequently detected

Investigation of pharmaceutical metabolites in environmental waters by LC-MS/MS

Pharmaceuticals, once ingested, are commonly metabolized in the body into more polar and soluble forms. These compounds might not be completely removed in the wastewater treatment plants and consequently being discharged into the aquatic ecosystem. In this work, a multi-class sensitive method for the analysis of 21 compounds, including 7 widely consumed pharmaceuticals and 14 relevant metabolites, has been developed based on the use of UHPLC-MS/MS in selected reaction monitoring (SRM) mode. The method was validated in six surface waters (SW) and six effluent wastewaters (EWW) at realistic concentration levels that can be found in waters. The optimized method was applied to the analysis of different types of water samples (rivers, lakes and effluent wastewater), detecting nearly all the parent compounds and metabolites investigated in this work. This fact illustrates that not only pharmaceuticals but also their metabolites are commonly present in these types of waters. Analytical research and monitoring programs should be directed not only towards parent pharmaceuticals but also towards relevant metabolites to have a realistic overview of the impact of pharmaceuticals in the aquatic environment

Analytical key issues and challenges in the LC-MS/MS determination of antibiotics in wastewater

The research on antibiotics occurrence in the aquatic environment has become a hot topic in the last years due to their potential negative effects, associated to possible bacterial antibiotic-resistance, after continuous exposure to these compounds. Most of antibiotic residues are not completely removed in the wastewater treatment plants (WWTPs) and end up in the aquatic environment through treated wastewater (WW). The development of reliable analytical methodologies for the determination of antibiotics in influent (IWW) and effluent wastewater (EWW) is needed with different purposes, among others: monitoring their occurrence in the aquatic environment, performing environmental risk assessment, estimating removal efficiencies of WWTPs, or estimating the consumption of these compounds. In this paper, we perform an in-depth investigation on analytical key issues that pose difficulties in the determination of antibiotics in complex matrices, such as WW, and we identify challenges to be properly addressed for successful analysis. The analytical technique selected was liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), as it is the most powerful and widely applied at present for antibiotic residues determination. The mass spectrometric behavior of 18 selected antibiotics, the chromatographic performance, ion ratio variations associated to the sample matrix when using different precursor ions or protomers, and the macrolides adsorption to glass vial, were some of the issues studied in this work. On the basis of the detailed study performed, an analytical LC-MS/MS method based on sample direct injection has been developed for quantification of 18 antibiotics in IWW and EWW, allowing their determination at low ng L−1 levels.Funding for open access charge: CRUE-Universitat Jaume IDavid Fabregat-Safont acknowledges Ministerio de Universidades in Spain for his Margarita Salas postdoctoral grant (Ref. MGS/2021/15). Authors acknowledge financial support from General Directorate of Water (Conselleria de Agricultura, Desarrollo Rural, Emergencia Climática y Transición Ecológica) and Generalitat Valenciana (research group of excellence PROMETEO 2019/040). Authors also acknowledge to FACSA (Castelló, Spain) for the wastewater sample collection and the Ayuntamiento of Castelló for the authorization to collect wastewater samples from the WWTP of Castelló. Authors are very grateful to Alberto Celma for his comments on fluoroquinolones protomers evaluation

Application of liquid chromatography/mass spectrometry in assessment of potential use of azadirachtins (TreeAzin ™ ) against Asian longhorned beetle

Azadirachtins are natural triterpenoid compounds derived from Neem tree extracts with potential for use as systemic insecticides against invasive wood-boring insect pests. In this work, a sensitive and selective analytical method has been developed for the simultaneous determination of azadirachtin A and azadirachtin B (3-tigloylazadirachtol) in foliage and twigs of various tree species. Samples were mixed with C18 and primary-secondary amine (PSA), and extracted with acetonitrile. Then, an aliquot of the raw extract was 10-fold diluted with water and directly analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The method was validated in foliage and twig matrices of four different tree species (London Plane Tree, Red/Freemani Maple, Norway Maple and Sugar Maple) that are known hosts of the exotic invasive insect pest – Asian Longhorn Beetle (ALB). Analytical results for replicate (N = 5) samples, fortified at 0.01, 0.1 and 1 mg kg , showed good recoveries (86 – 119%) and precision (<20% RSD). The methodology was successfully applied to the analysis of 200 samples taken from a field experiment designed to investigate uptake, translocation and expression of azadirachtins in representative high-value urban trees followed by stem injection with TreeAzinTM

Perencanaan home industry “Trufie” banana chocolate truffle dengan kapasitas produksi 50 box @96 gram/hari

Banana chocolate truffle adalah salah satu jenis produk pangan yang terbuat dari bahan baku cokelat dengan bentuk bulat serta memiliki isian berupa campuran pisang dan bahan pembantu lainnya. Bahan pembuatan banana chocolate truffle adalah pisang, dark chocolate compound, oat, selai kacang, madu, garam dan kacang almond. Perencanaan unit pengolahan pangan banana chocolate truffle “Trufie” mempunyai kapasitas produksi sebesar 50 box per hari. Unit pengolahan pangan banana chocolate truffle “Trufie” terletak di Jalan Manyar Jaya Praja III/D-23, Surabaya. “Trufie” merupakan Industri Rumah Tangga golongan UMKM. Struktur organisasi yang digunakan dalam perusahaan adalah struktur organisasi lini yang terdiri dari satu pimpinan dan dua karyawan. Garis besar proses pengolahan terdiri dari penimbangan, pencampuran, pembentukan, pendinginan I, pelapisan, pendinginan II dan pengemasan. Kemasan “Trufie” berupa box dengan bahan buffalo bersekat enam dengan wadah banana chocolate truffle di dalamnya. Utilitas yang diperlukan meliputi listrik 624 kWh/tahun, air 46,20 m3 /tahun dan 3 tabung LPG 12 kg/tahun. Pendirian usaha mempunyai laju pengembalian (ROR) setelah pajak sebesar 64% yang lebih tinggi daripada nilai MARR yaitu sebesar 12%. Waktu pengembalian modal setelah pajak adalah 18 bulan. Titik impas (BEP) yang diperoleh adalah 66,8%. Berdasarkan faktor teknik dan ekonomi, unit pengolahan pangan banana chocolate truffle “Trufie” layak didirikan

Screening of Pharmaceuticals and Illicit Drugs in Wastewater and Surface Waters of Spain and Italy by High Resolution Mass Spectrometry using UHPLC-QTOF MS and LC-LTQ-Orbitrap MS

The existence of pharmaceuticals and illicit drugs (PIDs) in environmental waters has led many analytical chemists to develop screening methods for monitoring purposes. Water samples can contain a huge number of possible contaminants, commonly at low concentrations, which makes their detection and identification problematic. Liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) has proven itself effective in the screening of environmental contaminants. The present work investigates the use of the most popular HRMS instruments, quadrupole time-of-flight and linear trap quadrupole-Orbitrap, from two different laboratories. A suspect screening for PIDs was carried out on wastewater (influent and effluent) and surface water samples from Castellón, Eastern Spain, and Cremona, Northern Italy, incorporating a database of 107 PIDs (including 220 fragment ions). A comparison between the findings of both instruments and of the samples was made which highlights the advantages and drawbacks of the strategies applied in each case. In total, 28 compounds were detected and/or identified by either/both instruments with irbesartan, valsartan, benzoylecgonine and caffeine being the most commonly found compounds across all samples

Flexible high resolution-mass spectrometry approach for screening new psychoactive substances in urban wastewater

The number of new psychoactive substances (NPS) on the recreational drug market has increased rapidly in the last years, creating serious challenges for public health agencies and law enforcement authorities. Epidemiological surveys and forensic analyses to monitor the consumption of these substances face some limitations for investigating their use on a large scale in a shifting market. The aim of this work was to develop a comprehensive and flexible screening approach for assessing the presence of NPS in urban wastewater by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Almost 200 substances were selected as “priority NPS” among those most frequently and recently reported by the Early Warning Systems (EWS) of different agencies and were included in the screening. Wastewater samples were collected from several cities all over Europe in 2016 and 2017, extracted using different solid-phase cartridges and analysed by LC-HRMS. The screening workflow comprised two successive analytical steps and compounds were identified and confirmed following specific criteria from the current guidelines. Thirteen NPS were identified at different confidence levels by using analytical standards or information from libraries and literature, and about half of them were phenethylamines. As far as we know, this is the first time that four of them (i.e. 3,4-dimethoxy-α-pyrrolidinovalerophenone, para-methoxyamphetamine, 2-phenethylamine and α – methyltryptamine) have been found in urban wastewater. The proposed screening approach was successfully applied in the largest NPS European wastewater monitoring, providing an innovative and easily adapted procedure for investigating NPS. In the light of current challenges and specific future research issues, this approach may complement epidemiological information and help in establishing measures for public health protection

PENYULUHAN PERAWATAN KULIT LANSIA DI MASA PANDEMI COVID-19 PADA PANTI SOSIAL

Abstrak: Penuaan menyebabkan kerusakan organ, termasuk kulit, menyebabkan berbagai masalah kesehatan di usia tua. Xerosis merupakan masalah yang sering terjadi, dimana prevalensinya berkisar 29% hingga 85%. Penggunaan hand sanitizer dan cuci tangan di era pandemi COVID-19 sangat penting, namun hal ini merupakan penyebab umum terjadinya xerosis dan iritasi terutama pada populasi lansia. Tujuan dilakukannya penyuluhan ini untuk mengatasi masalah yang berkaitan dengan kelainan kulit lansia pada masa pandemi COVID-19 melalui penyuluhan Perawatan Kulit Lansia di Masa Pandemi COVID-19. Tahapan pelaksanaan kegiatan pengabdian masyarakat ini adalah persiapan dengan melakukan koordinasi dengan Panti Sosial Tresna Werdha. Pelaksanaan penyuluhan dengan memberikan materi tentang cara perawatan kulit pada lansia yang didampingi tim pengabdi dan mahasiswa. Peserta kegiatan terdiri dari komunitas Panti Sosial Tresna Werdha yang berjumlah 33 peserta Hasil evaluasi menggunakan prepost test yang menunjukkan peningkatan pengetahuan. Pretest menunjukkan bahwa hanya 59% peserta yang mengetahui cara perawatan kulit pada lansia. Postest menunjukkan terjadi peningkatan sebanyak 85% setelah diberikan materi.Abstract: The aging process causes a decrease in organ function, including the skin, and causes various health problems in elderly. Pruritus is a complaint that is often found in old age. Xerosis is a common problem, with prevalence ranging from 29% to 85%. The use of hand sanitizers and washing hands in the era of the Covid-19 pandemic is of great importance and is therefore a common cause of dryness and inflammation in elderly patients. The purpose of this consultation is to overcome the problems related to skin diseases in the elderly during the Covid-19 pandemic.This can be achieved through advice on skin care for the elderly during the Covid-19 pandemic. The implementation phase of this community service is being prepared in coordination with the Tresna Werdha Social Institution. Provided materials on skin care for the elderly, accompanied by a team of volunteers and students to conduct consultations. The activity consisted of the Tresna Werdha, Social Institution community, totaling 33 participants. The evaluation results used a prepost test which showed an increase in knowledge. The pretest showed that only 59% of the participants knew how to care for their skin in the elderly. Posttest showed an increase of 85% after being given the material