High-performance Liquid Chromatography-tandem Mass Research Articles

Nontargeted lipidomics of Florida seagrasses

Seagrasses are one of the most productive foundation species in the world and are important for maintaining ecosystem homeostasis. However, seagrasses have experienced a global decline in areal extent, due in part to environmental stressors. Despite ongoing decline, little is known about the lipidome of most seagrass species. Generally, lipidome profiles closely align with phenotypic changes and can be used to evaluate the condition of an individual. In this study, a nontargeted lipidomics approach, utilizing high-performance liquid chromatography tandem mass spectrometry, was used to assess the lipidome of wild seagrasses in Florida. Overall, 399 individual lipid species, comprised of 33 lipid subclasses, were identified across all specimens. The lipid classes with the highest total concentration, accounting for 75% of total identified lipids in all seagrasses were: monogalactosyldiacylglycerols (MGDG), digalactosyldiacylglycerols (DGDG), and sulfoquinovosyl diacylglycerols (SQDG). Here, the lipidomic profiles of wild seagrasses were identified for the first time, a necessary step toward using lipodomics as a tool for prospective assessments of condition. Once regional and species-specific baselines have been mapped, lipodomic surveys could provide new insight into the effects of environmental stressors on seagrass condition and help to augment ongoing efforts to document and understand seagrass ecosystem status and trends.

Dissipation behaviours, residues, and health risk of six herbicides in sugar beets under field conditions

This study established a residue detection method based on the QuEChERS pre-treatment method and combined it with high-performance liquid chromatography–tandem mass spectrometry to test six herbicides (metamitron, clopyralid, desmedipham, phenmedipham, ethofumesate, and haloxyfop-p-methyl) in sugar beet plants, soil, and roots. The degradation dynamics and terminal residues of each herbicide in sugar beets were analysed. Finally, the dietary risks of various herbicides in sugar beets were evaluated based on the dietary structure of Chinese people, and the risk quotient values were below 100%. Using this detection method, all reagents exhibited good linearity (0.9724 ≤ R2 ≤ 0.9998), The limit of quantification (LOQ) ranged from 0.01 to 0.05 mg/L, the matrix effect ranged from −1.2% to −50%, the addition recovery rate ranged from 77.00% to 103.48%, and the relative standard deviation ranged from 1.61% to 16.17%; therefore, all indicators of this method met the residue detection standards. Under field conditions, the half-lives (t1/2) ranged about 0.65 ∼ 2.96 d and 0.38 ∼ 27.59 d in sugar beet plants and soil, respectively. All herbicides were easily degraded in sugar beet plants and soil (t1/2 < 30 d). The terminal residue amounts in the beet plants, soil, and roots ranged from < LOQ to 0.243 mg/kg. The dietary risk assessment of each pesticide was conducted based on the residual median of the terminal residues and the highest residual values on the edible part of the beetroot. The chronic exposure risk quotient (RQc) and acute exposure risk quotient (RQa) values were < 100%, indicating that the residue of each pesticide in beetroot posed low risks to consumers in China at the recommended dosage.

Metabolite profiling of triterpene saponins from different red beetroot cultivars using ultra-high performance liquid chromatography high-resolution mass spectrometry

In recent years, there has been increasing interest in the use of red beets as a valuable source of bioactive compounds. Although saponins may be responsible for the pharmacological and nutraceutical activities of red beets, information on the saponin composition of various red beet cultivars is very limited, and the saponin profiles remain to be fully elucidated. Here, we profiled triterpene saponins from the flesh and skin of different red beetroot cultivars, whose names of Polish cv. are Bonel, Chrobry and Nochowski. In addition, the total triterpene saponin contents in cultivars Bonel, Chrobry, Nochowski and in their various root parts were determined. Triterpene saponins isolated from the skin and flesh of different red beetroot cultivars were qualitatively profiled using two high-performance liquid chromatography systems (HPLC-ESI-IT MS and UPLC-HESI-Q-Orbitrap MS). The total triterpene saponin contents in different cultivars were analyzed using high-performance liquid chromatography-tandem mass spectrometry. In total, 40 triterpene saponins were tentatively identified, and among them, 5 compounds were potentially new saponins, not previously reported in red beets. These saponins are new to red beets and were reported in B. vulgaris for the first time. The analyzed cultivars were different in terms of their total saponin content. The results of our study indicated that the variation in the composition of saponins depended on the red beet cultivars and part of the roots. Higher concentrations of these compounds were found in the skins than in the flesh of roots. We developed an analytical strategy to discover and identify triterpene saponins from B. vulgaris L. using a combination of techniques to detect the comprehensive fragmentation pathways of the saponins present at low concentrations in plant material.

A survey on the current situation of serum vitamin A and vitamin D levels among children aged 2-

Objective: To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China. Methods: A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors. Results: The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A (χ2=7.91 and 8.06, both P=0.005) and vitamin D (χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively (OR=0.68 and 0.22, 95%CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB (χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively (χ2=93.22 and 202.54, both P<0.001). Conclusions: Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.

Development of a method for the determination of sedatives in bovine and porcine urine and kidneys by liquid chromatography–tandem mass spectrometry

Abstract Introduction Sedatives have been used for a long time as animal tranquillisers to prevent stress and weight loss during their transportation. The proper determination of these substances in food of animal origin is essential for consumer safety. Material and Methods A 1 g portion of pig or cow urine or homogenised kidney was mixed with acetonitrile, sodium chloride was added, and the solution was further mixed and then centrifuged. The supernatant was transferred to a new centrifuge tube with primary and secondary amine, octadecylsilane and ZrO2, and mixed rapidly. The filtered solution was evaporated under a nitrogen stream. The residue was dissolved in 200 μL of acetonitrile, centrifuged with filters and then transferred to vials. Samples were analysed by high-performance liquid chromatography–tandem mass spectrometry. Results The decision limit for confirmation was calculated at 2.5 μg kg−1 for all sedatives with relative standard deviation repeatability and reproducibility below 20%. Conclusion The validation results showed that this method meets the pertinent EU criteria for such methods and is suitable for sedative analysis in urine and kidney matrices.

Insufficiency of plasmatic arginine/homoarginine during the initial postoperative phase among patients with tumors affecting the medulla oblongata heightens the likelihood of neurogenic pulmonary oedema following surgery.

This prospective clinical study aims to investigate the fluctuations of neurotransmitters in peripheral venous blood during the perioperative period and to identify independent predictors for postoperative neurogenic pulmonary oedema (NPE) in patients with medulla oblongata-involved tumours. Peripheral venous blood samples of the enroled patients at seven perioperative time points, as well as their medical records and radiologic data were collected. High-performance liquid chromatography-tandem mass spectrometry was utilized to detect the concentrations of 39 neurotransmitters in these samples. The study applied univariate and multivariate generalized estimating equation (GEE) logistic regression analyses to explore independent predictors of postoperative NPE, and one-way repeated-measures ANOVA to compare the concentrations of the same neurotransmitter at different perioperative time points. The study included 36 patients with medulla oblongata-involved tumours from January to December 2019, and found that 13.9% of them experienced postoperative NPE. The absence of intraoperative use of sevoflurane ( P =0.008), decreased concentrations of arginine ( P =0.026) and homoarginine ( P =0.030), and prolonged postoperative tracheal extubation ( P <0.001) were identified as independent risk factors for postoperative NPE in medulla oblongata-involved tumour patients. Pairwise comparison analysis revealed that the perioperative decreases in arginine and homoarginine concentrations mainly occurred within the postoperative 8 h. This study demonstrates that NPE is not uncommon in patients with medulla oblongata-involved tumours. The absence of intraoperative use of sevoflurane, decreased concentrations of plasmatic arginine and homoarginine, and prolonged postoperative tracheal extubation are independent predictors of postoperative NPE. These two neurotransmitters' concentrations dropped mainly within the early postoperative hours and could serve as potential early warning indicators of postoperative NPE in clinical practice.

Optimization of enantioselective high-performance liquid chromatography-tandem mass spectrometry method for the quantitative determination of 3,4-methylenedioxy-methamphetamine (MDMA) and its phase-1 metabolites in human biological fluids

Recently we published in this journal an enantioselective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative determination of 3,4-methylenedioxymethamphetamine (MDMA) and its major phase-1 metabolites, 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy-3-methoxymethamphetamine (HMMA) and 3,4-methylenedioxyamphetamine (MDA) in human plasma, sweat, oral fluid and urine. Since we did not achieve simultaneous enantioseparation of all 4 compounds with a single chiral column, two amylose-based chiral columns were used alternatively. Further optimization of the mobile phase in the present study enabled baseline separation of all four pairs of enantiomers on a single Lux AMP column. In addition, by optimization of the column dimension and applied flow-rate it became possible to complete the separation within 6 minutes. These new methods were applied to the analysis of human plasma, oral fluid and urine. While results on the concentration of MDMA and its metabolites in various biological fluids were reported in our recent publication, in the present study an attempt was made to hydrolyze glucuronides in urine samples by using alternatively, hydrochloric acid or glucuronidase and to evaluate the effect of hydrolysis on the concentration and enantiomeric distribution of hydroxy metabolites of MDMA such as HMA and HMMA.

Development of a continuous magnetic dispersive solid phase extraction method for the extraction of seven widely used pesticides from fruit juices

Generally, food safety monitoring is vital issue to preserve human health and guarantee a longer lifespan. In present study, a continuous mode of magnetic dispersive solid phase extraction method based on using magnetic covalent organic framework@metal organic framework nanocomposite as sorbent has been proposed. The developed method has been tested for the extraction of some pesticides (pirimicarb, terbutryn, fenthion, triticonazole, hexaconazole, diniconazole, and haloxyfop-R-methyl) from commercial fruit juices prior to their analysis by high performance liquid chromatography–tandem mass spectrometry. In the current research, the properties of nanocomposite were characterized by scanning electron microscopy, Fourier–transform infrared spectrophotometry and X–ray diffraction techniques. In the next step, the synthesized nanocomposite was employed as an efficient sorbent in the developed extraction procedure that was done in a narrow bore tube. Under optimum extraction conditions, extraction recoveries were in the ranges of 67–83 %. Moreover, the limits of detection and quantification of the selected analytes were in the ranges of 17–43 and 56–143 ng L−1, respectively. Finally, the proposed method was successfully applied in the analysis of the opted pesticides in sixty fruit juice samples.

Valvular Prostaglandins Are Elevated in Severe Human Aortic Valve Stenosis.

Aortic valve stenosis (AVS) is the most common valvular disease in the developed world. AVS involves the progressive fibrocalcific remodeling of the aortic valve (AV), which impairs function and can ultimately lead to heart failure. Due to gaps in our understanding of the underlying mechanisms of AVS, there are no pharmacological treatments or dietary interventions known to slow AVS progression. Recent studies have begun to suggest oxylipins-a class of bioactive lipids-may be dysregulated in the valves of patients with AVS. We utilized high-performance liquid chromatography-tandem mass spectrometry to conduct a targeted oxylipin analysis on human AV tissue and plasma from a cohort of 110 patients undergoing AV surgery. We identified 36 oxylipins in human AV tissue with all showing significant increase in patients with severe AVS. A multivariate model including patient characteristics and valvular oxylipins identified the arachidonic acid-COX (cyclooxygenase) pathway-derived prostanoids to be the most associated with AVS severity. Plasma oxylipin levels were measured in a subset of AV surgery patients and compared with a control group of healthy participants, showing distinct oxylipin profiles between control and disease. Our comprehensive analysis of oxylipins in the human AV identified the inflammatory and osteogenic regulating prostanoids to be positively correlated with AVS severity. This elucidation of prostanoid dysregulation warrants further research into COX inhibition to mitigate AVS.

Comparison of Plasma Concentration of Linezolid's Detection by FICA and LC-MS/MS.

Linezolid was the first totally synthetic oxazolidinone antibiotic that was approved for clinical use against Mycobacterium tuberculosis. Our study investigated the correlation and consistency of fluorescence immunochromatography assay (FICA) and high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in measuring linezolid levels in the plasma. Plasma samples were collected from 80 to 100 tuberculosis patients. The samples were analyzed by FICA and LC-MS/MS, and linezolid levels measured by the two methods were compared by outlier test, correlation coefficient, Bland-Altman scatter plot, Deming regression analysis and bias evaluation. A total of 83 plasma samples were collected, all of which were non-outlier. The correlation coefficient of FICA and LC-MS/MS results was 0.9845. Deming regression analysis showed that the regression equation of FICA and LC-MS/MS was y = 0.2229 + 1.0076x. The medical decision levels of 2 and 7μg/mL were taken into the regression equation, and the 95% CI of 2- and 7-μg/mL bias were both within the allowed error range. The findings indicated a strong correlation between the results obtained from FICA and LC-MS/MS were consistent showed good correlation, demonstrating their equivalence in measurement.

Safety, Tolerability, and Pharmacokinetics of Voriconazole for Injection in Two Preparations in Chinese Healthy Adult Volunteers.

Voriconazole is a second-generation, synthetic, triazole antifungal drug based on the structure of fluconazole. We compared the safety, tolerability, and pharmacokinetic characteristics of voriconazole for injection (200mg) manufactured by at a dose of 6mg/kg in Chinese healthy adult volunteers. This was a single-center, randomized, open, 2-preparation, single-dose, 2-period, 2-sequence, crossover bioequivalence clinical trial. Twenty-four eligible, healthy, male, and female volunteers were assigned randomly to one of 2 dose-sequence groups (test-reference group or reference-test group) in a 1:1 block. The voriconazole concentration in plasma was determined by protein precipitation and high-performance liquid chromatography-tandem mass spectrometry. The main PK parameters were calculated on the basis of a noncompartmental model. The ratio of the geometric mean of the maximum plasma drug concentration, area under the plasma concentration-time curve from time 0 to the last time of quantifiable concentration, and area under the plasma concentration-time curve from time 0 to infinity of the test preparation, and the reference preparation was 100.4%, 102%, and 102.2%, respectively. The 90% confidence intervals were between 80% and 125%, indicating that the 2 preparations were bioequivalent. The adverse events experienced by healthy adult volunteers were mild. Both preparations had a good safety profile.

A New Ultra High-Performance Liquid Chromatography-Tandem Mass Spectrometry Method to Monitor 1-Amino-4-Methyl-Piperazine and 1-Methyl-4-Nitroso-Piperazine in Rifampicin Hydrolysis: A Standard Addition Approach to Quantify Nitrosamine in Rifampicin

1-amino-4-methyl-piperazine (AMP) is both a starting material for the synthesis of rifampicin (RIF) and a degradation product of RIF hydrolysis. 1-methyl-4-nitroso-piperazine (MNP) is an oxidation product of AMP as well as a potentially genotoxic N-nitrosamine. The EMA and FDA have approved an ad interim limit of 5 ppm for MNP in RIF drug products. As in-house methods for the analysis of MNP in RIF use a wide range of conditions for mobile phases and sample diluents, we decided to investigate whether these conditions affect the formation of MNP and AMP. A UHPLC-MS/MS method was developed to simultaneously quantify AMP and MNP during RIF hydrolysis in buffered aqueous solutions at different pH levels. Analyses were performed in MRM mode; separations were carried out on an InfinityLab Poroshell HPH-C18 (100 mm, 2.1 mm i.d., particle size 1.9 μm). In aqueous RIF solutions, the content of AMP and MNP increases with time; at different pHs, the concentration of AMP increases much faster in acidic than in basic solutions; and the increase in MNP can be reduced by the addition of ascorbic acid. To avoid an overestimation of MNP, water should not be used as a diluent in RIF sample preparations. Methanol is a more suitable diluent than water. A standard addition method has been validated for the quantification of MNP in RIF drug substances.

Determination of seven perfluoroalkyl and polyfluoroalkyl substances in serum of pregnant women and evaluation of neonatal neurobehavior based on high performance liquid chromatography-tandem mass spectrometry

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively used as synthetic fluorine-containing compounds in various consumer products, including surfactants, cookware, lubricants, clothing, and food packaging, since the 1950s. Evidence has shown that PFASs cross the placental barrier and interfere with fetal thyroid hormone homeostasis, which is crucial for fetal growth and neurobehavioral development in children aged 2-9 years. However, no epidemiological data on the association between prenatal PFAS exposure and neonatal neurobehavioral development are available. In this study, we explored the association between prenatal PFAS exposure and neonatal neurobehavioral development based on the Ezhou cohort study. Blood samples (10 mL) were collected during the third trimester of pregnancy (28-36 weeks) at the Ezhou maternal and child health hospital. The blood specimens were centrifuged at 4000 r/min for 15 min immediately after collection, separated, stored at -80 ℃. The samples were analyzed for seven PFASs, namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonamide (PFOSA). The PFASs were separated using a C18 column (100 mm×2.1 mm, 1.7 μm) at an oven temperature of 40 ℃, injection volume of 10 μL, and flow rate of 0.4 mL/min via gradient elution with methanol and ammonium acetate aqueous solution. The instrument was operated in negative electrospray ionization mode with multiple reaction monitoring. The correlation coefficients (r2), limits of detection (LODs) and quantification (LOQs), and spiked recoveries of the seven PFASs were 0.993-0.999, 0.006-0.020 ng/mL, 0.020-0.066 ng/mL, and 84.6%-116.8%, respectively. Neonatal behavioral neurological assessment (NBNA) was used to evaluate newborn cognitive development 72 h after birth; this tool consisted of five clusters, including behavior (six items), passive muscle tone (four items), active muscle tone (four items), primitive reflexes (three items), and general assessment (three items). Each item was rated on a three-point scale (0, 1, or 2), with the 20 items having a maximum score of 40. A total of 379 mother-newborn pairs were included in the analysis. The PFASs with the highest exposure levels was PFOA, with median levels of 19.4 ng/mL. Linear regression models were used to test the effects of ln-converted PFAS levels in newborns. After adjusting for confounding factors, the linear regression model showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(β(95% CI): 0.36(-0.64, 0.08)) and general assessment(β(95% CI): 0.34(-0.61, 0.07)) in all newborns. Furthermore, PFNA exposure was associated with decreased passive muscle tone(β(95% CI): 0.38(-0.74, 0.01)) and total NBNA(β(95% CI): 0.37(-0.68, 0.06)). PFDA exposure was associated with decreased behavior(β(95% CI): 0.28(-0.54, 0.01)), while PFHxS exposure was associated with elevated total NBNA(β(95% CI): 0.27(0.05-0.48)). Gender stratification analysis showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(β(95% CI): 0.54(-0.73, 0.35)) and general assessment(β(95% CI): 0.50(-0.88, 0.13)), PFNA exposure during pregnancy was associated with decreased passive muscle tone(β(95% CI): 0.67(-1.2, 0.14)) and total NBNA(β(95% CI): 0.45(-0.91, 0.01)), PFDA exposure during pregnancy was associated with decreased behavior(β(95% CI): 0.44(-0.71, 0.17)), PFHxS exposure was associated with elevated total NBNA(β(95% CI): 0.41(0.02-0.80)) in male newborns, and PFOA exposure was associated with decreased general assessment(β(95% CI): -0.27(-0.51, 0.02)), and PFDA exposure was associated with elevated behavior(β(95% CI): 0.46(0.40-0.52)) in female newborns. The proposed method separates and detects various PFASs without the need for cumbersome pretreatment processes, and has the advantages of low LODs, satisfactory recoveries, and accurate precision. Thus, it allows for the simultaneous analysis of trace PFASs in microserum samples from pregnant women. Our results also showed that prenatal PFAS exposure can lead to neurobehavioral disorders in offspring, with male newborns showing greater sensitivity than female newborns.

Association analysis between mixed exposure to phenols and semen quality

Phenols such as bisphenols, parabens, and triclosan are common environmental endocrine disruptors. Previous epidemiological studies have suggested that phenols may affect semen quality, but the results were inconsistent. In addition, most existing studies have been limited to the effects of a single chemical compound, ignoring the health effects of mixed exposure to multiple chemicals. Thus, we aimed to explore the associations between individual and mixed exposure to phenols and various semen quality parameters. In this study, a rapid and sensitive method was used to determine 18 phenolic compounds in urine samples of 799 volunteers who donated sperm samples to the Shanghai Human Sperm Bank. A spot urine sample was collected from each subject on the day of their clinic visit and stored at -20 ℃ until testing. Urine samples (200 μL) were extracted and added with 20 μL of an internal standard and 50 μL of β-glucuronidase solution. The mixtures were then incubated for 12 h at 37 ℃. After hydrolysis, the samples were extracted twice using ethyl acetate (500 μL). The concentrations of the 18 phenolic compounds were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Semen quality parameters were analyzed using a computer-aided semen analyzer. Multiple linear regressions were used to detect the associations between individual phenol exposure and semen quality parameters. In addition, weighted quantile sum (WQS) models were used to explore the associations between mixed-phenol exposure and semen quality parameters. After adjusting for potential covariates, the results of multiple linear regressions showed that exposure to ethyl paraben (EtP) was significantly negatively associated with sperm concentration and total sperm count (P<0.05). In addition, exposure to mixed phenols was significantly associated with decreased sperm concentration; methyl paraben (MeP) and EtP were identified as the main contributors to this decrease. Thus, phenol exposure may be associated with decreased semen quality in young males, particularly with respect to sperm concentration and total sperm count.

Определение диагностической значимости маркеров наследственных болезней обмена с применением метода хромато-масс-спектрометрии

Thorough investigation of metabolome by mass spectrometry is of great importance for personalized and preventive medicine. It is only timely laboratory diagnosis involving the use of high-tech chromatographic analysis methods that can help identify the patients with disorders of amino acid and acylcarnitine metabolism. The study was aimed to determine the efficacy of conventional and additional markers of metabolic disorders of amino acids and acylcarnitines detected by chromatography–mass spectrometry for the diagnosis of congenital metabolic disorders in children, as well as to create specific panels of the most effective indicators and determine the potential diagnostic efficacy of indentification of the relationships between the levels of amino acids and acylcarnitines in pediatric patients with congenital metabolic disorders. We assessed amino acid and acylcarnitine profiles in blood spots by high-performance liquid chromatography–tandem mass spectrometry in patients aged 6 months to 16 years (48 boys and 32 girls) with suspected aminoacidopathy and organic aciduria/acidemia. The comparison group consisted of 35 children with suspected peroxisomal metabolic disorders, the control group included 40 generally healthy children of various age groups. The data obtained were used to conduct the analysis of correlations between the groups of markers. Strong correlation was revealed for the levels of metabolically most closely related compounds (r &lt; 0.8, р &lt; 0.001). However, a similar relationship between metabolically not closely related compounds (correlation coefficient 0.45–0.73 (р &lt; 0.001)) was revealed for some groups of compounds. Thus, the acylcarnitine profile can be proposed as an additional potential marker to be used in cases of borderline phenylalanine levels, and the sum of normalized acylcarnitine levels (С12+С16) can be a potential secondary marker of phenylketonuria.

Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections.

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients. Methods: Seventeen elderly patients (age ≥ 65years) and six young critically ill patients (age < 65years) were enrolled. Six to eight blood samples were collected during the 12h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24h at steady state (AUCss, 0-24h). Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0-24h nor normalized AUCss, 0-24h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = -0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0-24h (r = -0.414, p = 0.049). Patients with AUCss, 0-24h ≥ 100mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0-24h < 50mg·h/L or patients with AUCss, 0-24h 50-100mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose. Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023.

2-Deoxyglucose and hydroxychloroquine HPLC-MS-MS analytical methods and pharmacokinetic interactions after oralco-administration in male rats.

Our previous work has shown a synergistic tumoricidal efficacy of combining the hexokinase (HK) inhibitor 2-deoxyglucose (2-DG) and the autophagy inhibitor chloroquine (CQ) through intraperitoneal injections on HK2-addicted prostate cancers in animal models. The pharmacokinetic (PK) behaviors of these oral drugs after simultaneous oral administration have not been reported. We developed high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analytical methods for 2-DG and the clinically favored drug hydroxychloroquine (HCQ) for sera samples. Using a jugular vein-cannulated male rat model with serial blood collection before and after a single gavage dose of each drug alone or in combination, we examined their PK metrics for drug-drug interactions. The data demonstrated a rapid and complete separation of 2-DG from common monosaccharides by HPLC-MS-MS multi-reaction monitoring. Application of the HPLC-MS-MS 2-DG and HCQ methods to sera samples of nine rats showed a peak time (Tmax ) for 2-DG of 0.5 h after 2-DG alone or with HCQ and identical post-peak half-life of approximately 1 h. With a seemingly bi-modal time course for HCQ, the Tmax for HCQ alone (1.2 h) was faster than that for the combination (2 h; p = .017). After combination dosing, the peak concentration (Cmax ) and area under the curve (AUC0-4h ) of 2-DG were decreased by 53.8% (p = .0004) and 53.7% (p = .0001), whereas AUC0-8h for HCQ was decreased by 30.8% (p = .0279) from the respective single dosing. Without changing the mean residence time (MRT0-∞ ) of each drug, the combination affected the apparent volume of distribution (Vd ) and clearance (CL) of 2-DG, and CL for HCQ without affecting its Vd . We observed significant negative PK interactions, probably at the intestinal absorption level, between 2-DG and HCQ taken simultaneously by mouth. Future optimization efforts are warranted for their combination regimen for clinical translation.

Association of serum trimethylamine N-oxide levels and bone mineral density in type 2 diabetes mellitus.

The relationship between trimethylamine N-oxide (TMAO) and bone mineral density (BMD) in type 2 diabetes mellitus (T2DM) is unclear. We explore the relationship between TMAO levels and BMD in T2DM. This is a cross-sectional study. 254 T2DM patients were enrolled and divided into three groups by TMAO tertiles, and the clinical data were collected. BMD was determined by dual-energy X-ray absorptiometry (DXA) and serum TMAO levels was determined by stable isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients in the highest tertile of TMAO levels (TMAO > 6.72 μmol/L) showed relatively low BMD and a higher number of fracture history, osteoporosis (OP) than those in the lower tertiles. Spearman correlation analysis showed that serum TMAO was negatively correlated with BMD of whole body (WB), lumbar spine (LS) and femoral neck (FN), while TMAO was positive correlated with osteoporotic fracture (p < 0.05). Logistic regression models showed that TMAO was an independent influencing factor of fracture history after adjusting for confounders in TMAO > 6.72 μmol/L group. There is a significant linear correlation between TMAO levels and BMD in T2DM patients. Especially in TMAO > 6.72 μmol/L group, TMAO was negatively correlated with WB, LS, and FN BMD, and was positive correlated with osteoporotic fracture in T2DM patients. The findings suggest that elevated TMAO levels are associated with OP and osteoporotic fracture in T2DM patients.

Formula model established through field application of glass slides and rapid analysis of pesticide residues in vegetables by ion mobility spectrometry

The prevalence of pesticide usage has brought the matter of pesticide residues to the forefront, necessitating the development of effective detection methods as a crucial step towards addressing this issue. This study presents a novel approach for detecting pesticide residues in vegetables using glass slide-formula-ion mobility spectrometry (IMS). The approach enables swift analysis of 36 different pesticides across three vegetable species with glass slides. To establish a formula for calculating pesticide residues in vegetables using glass slides, the vegetable samples and glass slides were placed in a spray tower and evenly sprayed pesticides. The per unit area of glass slides was used to calculate the pesticide loading capacity and total pesticide loading area of vegetables. The original residues were analyzed with ultra high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The field experiment yielded consistent results between the model values of the formula and the actual measured values, with correlation coefficients (R2) ranging from 0.927 to 0.983. The slide-formula model-IMS method was found to be effective for field applications, as it proved to be simple, rapid, and accurate in predicting pesticide residue concentrations in vegetable samples. This approach could be a valuable tool for monitoring pesticide residues in vegetable cultivation globally.

Effects of vitamin C on the pharmacokinetics and pharmacodynamics of nimodipine in rats.

In recent years, researchers have shown a growing interest in the interactions between different pharmaceutical agents. An intriguing instance lies in the possible interaction between nimodipine and vitamin C. To investigate the pharmacokinetic and pharmacodynamic effects of vitamin C on nimodipine in rats, rats were randomly divided into a nimodipine only group and a combination group (nimodipine + vitamin C). The two groups were given intragastric administration and nimodipine blood concentrations were determined using high-performance liquid chromatography-tandem mass spectrum at different time points. Blood pressure and heart rate were measured via carotid artery cannulation. Pharmacokinetic differences were observed between the nimodipine only group and the combination group at the same dose. Compared with the nimodipine only group, the combination group's main pharmacokinetic parameters of peak concentration and area under the curve increased significantly, and the difference was statistically significant (p < 0.05); furthermore, the combination group exhibited a significant reduction in average blood pressure, while no significant effects on heart rate were observed. Vitamin C did not affect the activity of CYP450 in rat liver. The pharmacokinetic characteristics and pharmacodynamics of nimodipine were changed by vitamin C administration in rats.