Performance Liquid Chromatography-tandem Mass Research Articles

Exploration of emerging environmental pollutants 6PPD and 6PPDQ in honey and fish samples

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPDQ) can pose a threat to human health through the food chain because of their ubiquitous presence in the environment and the biotoxicity on organisms. In this work, we developed modified QuEChERS methods coupled with high performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS) to explore whether 6PPD and 6PPDQ are present in fish and honey. The proposed methods showed acceptable limits of quantification (0.00043-0.001 mg/kg), linearity (R2 > 0.99), recovery (73.3%-108.3%), matrix effect (70.4%-95.6%) and repeatability (RSD < 8.4%). Accordingly, 6PPD and 6PPDQ have been discovered in snakehead, weever and Spanish mackerel fish, while none of which have been detected in the honey samples. The results of our work contributed to increasing public attention to 6PPD and 6PPDQ in agricultural products and provided important reference for the analysis of them.

Physiologically Based Pharmacokinetic Modeling of Vitamin D3 and Metabolites in Vitamin D-Insufficient Patients.

A physiologically based pharmacokinetic (PBPK) model of vitamin D3 and metabolites [25(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3] is presented. In this study, patients with 25(OH)D3 plasma concentrations below 30 ng/ml were studied after a single dose of 5000 I.U. (125 µg) cholecalciferol, provided with 5000 I.U. daily cholecalciferol supplementation until vitamin D replete [25(OH)D3 plasma concentrations above 30 ng/ml], and had serial plasma samples were collected at each phase for 14 days. Total concentrations of vitamin D3 and metabolites were measured by ultra-high performance liquid chromatography tandem mass spectrometry. A nine-compartment PBPK model was built using MATLAB to represent the triphasic study nature (insufficient, replenishing, and sufficient). The stimulatory and inhibitory effect of 1,25(OH)2D3 were incorporated by fold-changes in the primary metabolic enzymes CYP27B1 and CYP24A1, respectively. Incorporation of dynamic adipose partition coefficients for vitamin D3 and 25(OH)D3 and variable enzymatic reactions aided in model fitting. Measures of model predictions agreed well with data from metabolites, with 97%, 88%, and 98% of the data for 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3, respectively, within twofold of unity (fold error values between 0.5 and 2.0). Bootstrapping was performed and optimized parameters were reported with 95% confidence intervals. This PBPK model could be a useful tool for understanding the connections between vitamin D and its metabolites under a variety of clinical situations. SIGNIFICANCE STATEMENT: This study developed a physiologically based pharmacokinetic (PBPK) model of vitamin D3 and metabolites for patients moving from an insufficient to a repleted state over a period of 16 weeks.

Alpha-chloralose poisoning in cats: clinical findings in 25 confirmed and 78 suspected cases

ObjectivesThe aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning.MethodsSuspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat’s intoxication severity score.ResultsSerum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time <48 h, irrespective of intoxication severity score.Conclusions and relevanceThis study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia.

Rapid quantitative analysis of 12 chemical constituents in wild-simulated and cultivated Astragali Radix based on UHPLC-MS

ObjectiveAstragali Radix (AR) is one of the most widely used traditional Chinese medicines (TCMs) for tonic, which can be divided into wild-simulated and cultivated AR according to its cultivation method. However, whether cultivated AR can replace wild-simulated AR has always been a concern. MethodsIn this study, a rapid, highly sensitive and specific analytical method using ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS) was developed to quantitatively measure 12 chemical constituents of AR in the different cultivation methods. ResultsAR samples were analyzed with a good linear regression relationship (R2, 0.9983–0.9995), precisions (relative standard deviation (RSD), 1.31%−2.36%), repeatability (RSD, 2.65%−4.92%), stability (RSD, 1.50%−4.05%), and recovery (95.13%−106.52%). Through the determination of AR samples, we found the components of flavonoids in wild-simulated AR were higher than cultivated AR, the saponins in cultivated AR were higher, the ratio of saponins/flavonoids in cultivated AR was higher than wild-simulated AR. ConclusionBased on this research, it could provide guidance for the quality control of AR.

Pharmacokinetics Study of Jin-Gu-Lian Prescription and Its Core Drug Pair (Sargentodoxa cuneata (Oliv.) Rehd. et W and Alangium chinense (Lour.) Harms) by UPLC-MS/MS.

Jin-Gu-Lian (JGL) is traditionally used by Miao for the treatment of rheumatism arthralgia. At the same time, the combination of Sargentodoxa cuneata (Oliv.) Rehd. et W (SC) and Alangium chinense (Lour.) Harms (AC), the core drug pair (CDP) in the formula of JGL, is used at high frequencies in many Miao medicine prescriptions for rheumatic diseases. However, previous research lacks the pharmacokinetic study of JGL, and study on the compatibility of its CDP with other medicinal herbs in the formula is needed. This study aims to establish a simple, rapid, and sensitive Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous determination of four main bioactive components of JGL in rat plasma, including Salidroside (Sal), Anabasine (Ana), Chlorogenic Acid (CA), and Protocatechuic Acid (PCA), and compare the pharmacokinetic properties of two groups of rats after being orally administrated with JGL and its CDP extracts, respectively. The results showed that area under the plasma concentration-time curve (AUC), mean retention time (MRT), and clearance rate (CL), of Sal, Ana, CA and PCA in the two groups of rats were changed in different degrees. The CDP combined with other drugs could significantly increase the absorption of Sal and Ana, prolong its retention time in vivo, and may accelerate the absorption rate of CA and PCA. This indicated that the combination of CDP and other herbs may affect the pharmacokinetics process of active components in vivo, increase the exposure and bioavailability of compounds in the JGL group, and prolong the retention time, which may be the reason why JGL has a better inhibitory effect on inflammatory cytokines, providing a viable orientation for the compatibility investigation of herb medicines.

Distribution and Ecological Risk Assessment of Pharmaceuticals and Personal Care Products in Sediments of North Canal, China

The pollution of water bodies by pharmaceuticals and personal care products (PPCPs) has attracted widespread concern due to their widespread use and pseudo-persistence, but their effects on sediments are less known. In this study, solid-phase extraction-high performance liquid chromatography–tandem mass spectrometry (SPE-LC/MSMS) was used to investigate the occurrence and ecological risks of five typical pharmaceuticals and personal care products (PPCPs) in thirteen key reservoirs, sluices, dams, and estuaries in the Haihe River Basin. At the same time, the PPCP exchanges of surface water, groundwater, and sediments in three typical sections were studied. Finally, the PPCP’s environmental risk is evaluated through the environmental risk quotient. The results showed that the five PPCPs were tri-methoprazine (TMP), sinolamine (SMX), ibuprofen (IBU), triclosan (TCS), and caffeine (CAF). The average concentration of these PPCPs ranged from 0 to 481.19 μg/kg, with relatively high concentrations of TCS and CAF. The relationship between PPCPs in the surface sediments was analyzed to reveal correlations between SMX and TMP, CAF and IBU, CAF and TCS. The risk quotients (RQ) method was used to evaluate the ecological risk of the five detected PPCPs. The major contributors of potential environmental risks were IBU, TCS and CAF, among which all the potential environmental risks at the TCS samples were high risk. This study supplemented the research on the ecological risk of PPCPs in sediments of important reaches of the North Canal to reveal the importance of PPCP control in the North Canal and provided a scientific basis for pollution control and risk prevention of PPCPs.

Degradation of carbamazepine by high-voltage direct current gas-liquid plasma with the addition of H2O2 and Fe2.

Carbamazepine (CBZ) is a typical psychotropic pharmaceutical which is one of the most commonly detected persistent pharmaceuticals in the environment. The degradation of CBZ in the aqueous solution was studied by a direct current (DC) gas-liquid phase discharge plasma combined with different catalysts (H2O2 or Fe2+) in this study. The concentrations of reactive species (H2O2, O3, and NO3-) and •OH radical yield in the liquid were measured during the discharge process. The various parameters that affect the degradation of CBZ, such as discharge powers, initial concentrations, initial pH values, and addition of catalysts, were investigated. The energy efficiency was 25.2mg·kW-1·h-1 at 35.7W, and the discharge power at 35.7W was selected to achieve the optimal balance on the degradation effect and energy efficiency. Both acidic and alkaline solution conditions were conducive to promoting the degradation of CBZ. Both H2O2 and Fe2+ at low concentration (10-100mg/L of Fe2+, 0.05-2.0mmol/L of H2O2) were observed contributing to the improvement of the CBZ degradation rate, while the promotional effect of CBZ degradation was weakened even inhibition would occur at high concentrations (100-200mg/L of Fe2+, 2.0-5.0mmol/L of H2O2). The degradation rate of CBZ was up to 99.1%, and the total organic carbon (TOC) removal efficiency of CBZ was up to 67.1% in the plasma/Fe2+ (100mg/L) system at 48min, which suggested that high degradation rate and mineralization efficiency on CBZ could be achieved by employing Fe2+ as a catalyst. Based on the intermediate products identified by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS), the possible degradation pathways were proposed. Finally, the growth inhibition assay with Escherichia coli (E. coli) showed that the toxicity of plasma/Fe2+-treated CBZ solution decreased and a relatively low solution toxicity could be achieved. Thus, the plasma/catalyst could be an effective technology for the degradation of pharmaceuticals in aqueous solutions.

Extension of the Temporal Window for the Determination of Alpha-Methylthiofentanyl and Thiofentanyl in Rat Urine by Monitoring the Metabolite Norfentanyl Using Online Solid-Phase Extraction (SPE) Coupled with Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC–MS/MS)

Alpha-methylthiofentanyl and thiofentanyl are psychoactive substances that have been abused in recent years, strongly threatening social and public security. Because they are rapidly metabolized in vivo, their determination presents a great challenge for forensic science. An automated method of online solid-phase extraction coupled with ultra-high performance liquid chromatography—tandem mass spectrometry was developed for the determination of alpha-methylthiofentanyl, thiofentanyl, and the metabolite norfentanyl in urine. The analytes were first enriched and purified by an Oasis HLB online SPE column and eluted on a Hypersil GOLD C18 analytical column. Chromatographic separation was achieved with mobile phase components of 2 mM ammonium formate and 0.1% formic acid in water and same composition in methanol in gradient elution mode. The limit of detection and lower limit of quantitation of the method for the three analytes were 0.2 and 2 pg/ml, respectively. Acceptable linearity was obtained from 2 to 800 pg/ml. The accuracy was in the range of 87.98–108.95%; and precision, calculated as the relative standard deviation, was less than 14.63%. The method recoveries were from 65.56 to 113.72%. This highly sensitive method was applied to study the detection window of the precursor compounds and metabolites in rat urine. Both alpha-methylthiofentanyl and thiofentanyl are metabolized to norfentanyl, which was first revealed in this study. With the aid of norfentanyl, the detection windows of alpha-methylthiofentanyl and thiofentanyl were extended to 18–26 days and 20–27 days, respectively. This study provides important auxiliary tools for the forensic identification of fentanyl analogs.

A green and rapid analytical method for determination of kitasamycin in animal feedstuffs by ultra-high performance liquid chromatography tandem mass spectrometry

A rapid, simple, highly efficiency analytical method for detecting kitasamycin A1, A4, A5, and A13 in different feedstuffs was successfully developed by combining enhanced matrix removal (EMR) lipid cartridge and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). After extraction with acetonitrile, the sample supernatants were directly passed through the EMR lipid cartridge. Then, the cartridge was rinsed and eluted with acetonitrile and methanol, respectively, followed by UHPLC-MS/MS analysis with positive mode using multiple reaction monitoring. Optimized pretreatment procedure without solvent conversion, multiple nitrogen drying steps and activated cartridge before loading, and no significant interference were found during the analysis of different types of animal feedstuffs. Excellent sensitivity (Limit of quantification, LOQ) of kitasamycin A1, A4, A5, and A13 was 1.1–2.0 µg/kg. Satisfactory recoveries of kitasamycin A1, A4, A5, and A13 in different feedstuffs were from 74.0% to 98.8%, with the relative standard deviations (RSDs) below 10.4%, and good linear correlation coefficient (r)>0.9990 in the matrix matched standard curve range of 0.02–50.0 µg/L. Results demonstrated that the developed method exhibited excellent linearity, accuracy, precision, sensitivity, and the feasibility of using this method in kitasamycin determination of animal feedstuffs. The method was evaluated using the greenness analysis method through Eco-Scale assessment tool.

Cefuroxime concentrations in the anterior and posterior column of the lumbar spine – an experimental porcine study

BACKGROUND CONTEXTSurgical site infection following spine surgery is associated with increased morbidity and mortality. Perioperative antibiotic prophylaxis is a key factor in lowering the risk of acquiring an infection. Previous studies have assessed perioperative cefuroxime concentrations in the anterior column of the cervical spine with an anterior surgical approach. However, the majority of surgeries are performed in the posterior column and many surgeries involve the lumbar spine. PURPOSEThe objective of this study was to compare the perioperative tissue concentrations of cefuroxime in the anterior and posterior column during lumbar spine surgery with a posterior surgical approach. STUDY DESIGNIn vivo experimental pharmacokinetic study of cefuroxime concentrations in an acute preclinical porcine model. METHODSThe lumbar vertebral column was exposed from L1 to L5 in 8 female pigs. Microdialysis catheters were placed for sampling in the anterior column (vertebral body) and posterior column (posterior arch) within the same vertebra (L5). Cefuroxime (1.5 g) was administered intravenously. Microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. The primary endpoint was the time above the cefuroxime clinical breakpoint minimal inhibitory concentration (T>MIC) for Staphylococcus aureus of 4 µg/mL. The secondary endpoint was tissue penetration (AUCtissue/AUCplasma). RESULTSMean T>MIC 4 µg/mL (95% confidence interval) was 123 min (105–141) in plasma, 97 min (79–115) in the anterior column and 93 min (75–111) in the posterior column. Tissue penetration (95% confidence interval) was incomplete for both the anterior column 0.48 (0.40–0.56) and posterior column 0.40 (0.33–0.48). CONCLUSIONST>MIC was comparable between the anterior and posterior column. Mean cefuroxime concentrations decreased below the clinical breakpoint minimal inhibitory concentration for S. aureus of 4 µg/mL after 123 minutes (plasma), 97 minutes (anterior column) and 93 minutes (posterior column). This is shorter than the duration of most lumbar spine surgeries, and therefore alternative dosing regimens should be considered in posterior open lumbar spine surgeries lasting more than 1.5 hours. CLINICAL SIGNIFICANCEOpen lumbar spine surgery often involves extensive soft tissue dissection, stripping and retraction of the paraspinal muscles which may impair the local blood flow exposing the lumbar vertebra to postoperative infections. A single intravenous administration of 1.5 g cefuroxime only provided sufficient prophylactic target tissue concentrations in the vertebra of the lumbar spine for up to 1.5 hours.

Association of serum bisphenol AF concentration with depressive symptoms in adolescents: A nested case–control study in China

BackgroundAs an important alternative to bisphenol A (BPA), bisphenol AF (BPAF) is widely used and can be detected in multiple human biological samples. However, there are few studies on neurotoxicity of BPAF at present. In particular, no epidemiological studies have investigated BPAF in relation to depressive symptoms in adolescents. Here, our study aimed to evaluate the associations between serum BPAF concentrations and depressive symptoms in adolescents. MethodsA nested case-control study within an ongoing longitudinal prospective adolescent cohort that was established in Huaibei, China was conducted. A total of 175 participants who had new-onset depressive symptoms (cases) and 175 participants without depressive symptoms (controls) were included. Serum BPAF concentrations was measured using ultra–high–performance liquid chromatography–tandem mass spectrometry. The associations between BPAF exposure and the risk of depressive symptoms in adolescents were assessed using conditional logistic regression. The dose-response relationship between BPAF level and depressive symptoms was estimated using restricted cubic spline analyses. ResultsIn this study, the detection rate of serum BPAF was 100%, and the median (interquartile range, IQR) serum BPAF concentration was 5.24 (4.41–6.11) pg/mL in the case group and 4.86 (4.02–5.77) pg/mL in the control group (P = 0.009). Serum BPAF exposure was a risk factor for depressive symptoms (odds ratio (OR)= 1.132, 95% confidence interval (CI):1.013–1.264). After adjustment for all for confounders, compared with the low–exposure group, the high–exposure group had a 2.806-fold increased risk of depressive symptoms (OR=2.806, 95% CI: 1.188–6.626). Stratified analysis by sex revealed that males were more vulnerable to BPAF exposure than females. After adjustment for all confounders, compared with the low-exposure group, the relative risk of depressive symptoms in the high-exposure group was 3.858 (95% CI: 1.118–12.535) for males, however, no significant association between BPAF exposure and depressive symptoms was found in females. In addition, there was a marked linear association between BPAF exposure and the risk of depressive symptoms in the total population and in males. ConclusionsThe adolescents in this study were widely exposed to low levels of BPAF. A significant positive association was found between serum BPAF levels and the risk of depressive symptoms. The association was significantly modified by sex, and males were more vulnerable to BPAF exposure than females.

Identification of differential metabolites using untargeted metabolomics between gestational diabetes and normal pregnant women.

To study the metabonomics differences between pregnant women with gestational diabetes mellitus (GDM) in the third trimester and those in a group without GDM by screening a group of highly efficient and sensitive markers for GDM and validating previously published early metabolic markers of GDM. A cross-sectional cohort study based on ultra performance liquid chromatography tandem mass spectrometry untargeted metabolomics analysis of serum samples collected from 59 pregnant women with GDM and 59 pregnant women without GDM. A total of 121 metabolites were detected, and 27 were identified as differential metabolites between GDM and control. The combination of 27 metabolic peaks had area under curve (AUC) values of 0.90, 0.92, and 0.93 in the prediction models using support vector machine, partial least squares, and random forest, respectively. Finally, five metabolite biomarkers were selected to construct logistic regression models: L-valine, hypoxanthine, eicosapentaenoic acid, 2-amino-1,3,4-octadecanotriol, and choline. The AUC value of these metabolites was 0.769 between the GDM group and the control group. The discovery of a group of differential metabolites in pregnant women with GDM in the third trimester and in pregnant women without GDM may facilitate the study of the pathologic mechanism of GDM; it may be possible to find an efficient and sensitive alternative GDM detection method.

Biotransformation and transplacental transfer of the anti-viral remdesivir and predominant metabolite, GS-441524 in pregnant rats.

SummaryBackgroundRemdesivir was the first prodrug approved to treat coronavirus disease 2019 (COVID-19) and has the potential to be used during pregnancy. However, it is not known whether remdesivir and its main metabolite, GS-441524 have the potential to cross the blood-placental barrier. We hypothesize that remdesivir and predominant metabolite GS-441524may cross the blood-placental barrier to reach the embryo tissues.MethodsTo test this hypothesis, ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) coupled with multisite microdialysis was used to monitor the levels of remdesivir and the nucleoside analogue GS-441524 in the maternal blood, fetus, placenta, and amniotic fluid of pregnant Sprague-Dawley rats. The transplacental transfer was evaluated using the pharmacokinetic parameters of AUC and mother-to-fetus transfer ratio (AUCfetus/AUCmother).FindingsOur in-vivo results show that remdesivir is rapidly biotransformed into GS-441524 in the maternal blood, which then readily crossed the placenta with a mother-to-fetus transfer ratio of 0.51 ± 0.18. The Cmax and AUClast values of GS-441524 followed the order: maternal blood > amniotic fluid > fetus > placenta in rats.InterpretationWhile remdesivir does not directly cross into the fetus, however, its main metabolite, GS-441524 readily crosses the placenta and can reside there for at least 4 hours as shown in the pregnant Sprague-Dawley rat model. These findings suggest that careful consideration should be taken for the use of remdesivir in the treatment of COVID-19 in pregnancy.FundingMinistry of Science and Technology of Taiwan.

Preclinical Pharmacokinetics and Bioavailability of Oxypeucedanin in Rats after Single Intravenous and Oral Administration.

Oxypeucedanin, a furanocoumarin extracted from many traditional Chinese herbal medicines, has a variety of pharmacological effects. However, the independent pharmacokinetic characteristics and bioavailability of this compound remains elusive. In this study, a rapid, sensitive, and selective method using ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC/MS/MS) was developed for evaluating the intravenous and oral pharmacokinetics of oxypeucedanin. After intravenous administration of oxypeucedanin (2.5, 5, and 10 mg/kg), and intragastric administration of oxypeucedanin (20 mg/kg), blood samples were collected periodically from the tail vein. The plasma concentration-time curves were plotted, and the pharmacokinetic parameters were calculated using a non-compartmental model analysis. After intravenous administration of oxypeucedanin (single dosing at 2.5, 5, and 10 mg/kg) to rats, the pharmacokinetics fit the linear kinetics characteristics, which showed that some parameters including average elimination half-life (T1/2Z of 0.61~0.66 h), mean residence time (MRT of 0.62~0.80 h), apparent volume of distribution (VZ of 4.98~7.50 L/kg), and systemic clearance (CLZ of 5.64~8.55 L/kg/h) are dose-independent and the area under concentration-time curve (AUC) increased in a dose-proportional manner. Single oral administration of oxypeucedanin (20 mg/kg) showed poor and slow absorption with the mean time to reach the peak concentration (Tmax) of 3.38 h, MRT of 5.86 h, T1/2Z of 2.94 h, and a mean absolute bioavailability of 10.26% in rats. These results provide critical information for a better understanding of the pharmacological effect of oxypeucedanin, which will facilitate its research and development.

Pharmacokinetics Study of Rabdosia rubescens Drop Pills Based on UPLC-MS/MS

Background: Rabdosia rubescens drop pills have the effects of clearing away heat and toxin, detumescence, relieving pain. Objective: A simple and sensitive method for simultaneous determination of oridonin, ponicidin, and rosmarinic acid in rat plasma was developed based on ultra performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS). Methods: Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) with a mobile phase consisting of water containing 0.2% formic acid (mobile phase A) and methanol (mobile phase B) at a flow rate of 0.3 mL/min over a total run time of 3.8 min. All analytes were measured with optimized multiple reaction monitoring (MRM) in positive and negative ion ESI mode. Results: The transitions of oridonin, ponicidin, rosmarinic acid, diphenhydramine, and chloramphenicol were 365.3→347.3, 363.3→345.2, 359.0→160.9, 256.0→167.2, and 321.1→151.9, respectively. The linear ranges were 1-256 ng/mL for ponicidin and rosmarinic acid and 2-512 ng/mL for oridonin. The validated method was stable and reliable. There was no significant difference in the half-life (t1/2) of the three analytes at three doses. The area under the curve (AUC0-t) and peak concentration (Cmax) of the three analytes decreased linearly in each dose range, and the linear correlation R2 of each analyte under the three doses was greater than 0.95. Conclusion: This method was successfully applied to pharmacokinetic studies of oridonin, ponicidin, and rosmarinic acid in rat plasma after intragastric administration of Rabdosia rubescens drop pills.

Application of an improved hollow fiber liquid phase microextraction technique coupled to LC-MS/MS to studying migration of fluorescent whitening agents from plastic food contact materials

In this paper, a new hollow fiber liquid-phase microextraction method was developed to improve the extraction of five fluorescent whitening agents that migrated from plastics food contact materials. Influencing factors, such as the types of membrane, the extraction solvent, the stirring speed, the addition of salt ion, and extraction time, were investigated in detail. Under the optimal conditions, high enrichment factors (71–205) can be obtained with 15 μL extraction solvent. The new method is advantageous; the polypropylene hollow fiber membrane modified by sepiolite nanoparticles had excellent solvent binding force and mass transfer effect compared with the conventional extraction technique. The extracts were analyzed by high performance liquid chromatography–tandem mass spectrometry, the limits of detection were 0.3 or 0.9 ng kg−1 with good correlation coefficients (r 2 ≥ 0.9940) for the five fluorescent whitening agents. The intra-day and inter-day recoveries ranged between 82.6% and 112%, with a relative standard deviation of less than 12%. The established method was successfully applied to the analysis of fluorescent whitening agent migration from four types of plastic food contact materials immersed in three food simulants.

Multi-residue analysis, dissipation behavior, and final residues of four insecticides in supervised eggplant field

In this study, the residues of four insecticides, spirotetramat, flonicamid, thiamethoxam, and tolfenpyrad, and their metabolites, including spirotetramat-enol, spirotetramat-mono-hydroxy, spirotetramat-keto-hydroxy, spirotetramat-enol-glucoside, 4-trifluoromethylnicotinamide, 4-trifluoromethylnicotinic acid, N-(4-trifluoromethylnicotinoyl) glycine, and clothianidin, were assessed using a single analysis method. The samples were extracted by acetonitrile, then purified by dispersive solid phase extraction and quantified using high performance liquid chromatography tandem mass spectrometry. The average recovery rate of 12 target compounds was 73.5–103.7%, the relative standard deviation was 1.1–18.3%, and the limit of quantification was 0.01–0.05 mg/kg. The results showed good linearity (R 2 >0.99), meeting the requirements of the pesticide residue analysis. The dissipation half-lives of the four insecticides in eggplant were 3.4–14.5 days. After the last applications at 7 and 10 days, the final residues of the four insecticides in eggplant were <0.01–0.21, 0.085–0.26, <0.05–0.078, and <0.01–0.21 mg/kg, respectively. The dissipation and final residue results could provide a theoretical basis for the rational application of four insecticides in eggplant fields. Highlights HPLC-MS/MS for simultaneous determination of four insecticides and their metabolites in eggplant fields. The dissipation dynamics and final residue of the target compounds in field eggplant were studied. Guidance for the safe use of four insecticides on eggplant.

Determination of free and encapsulated cytarabine and daunorubicin in rat plasma after intravenous administration of liposomal formulation using ultra-high performance liquid chromatography tandem mass spectrometry

Liposome encapsulating cytarabine (CYT) and daunorubicin (DNR) is applied for treating Acute Myeloid Leukemia (AML) patients. To evaluate and compare relationship between the pharmacokinetics of free drug (drug which is not entrapped in liposomes) and liposome-encapsulated drug and the toxicity/efficacy, it is crucial to have trustworthy methods for separating the free and the encapsulated of the drug. In this study, methods were developed and validated to isolate and measure the free DNR/CYT (F-DNR/CYT), the encapsulated DNR/CYT (E-DNR/CYT) and the total DNR/CYT (T-DNR/CYT) in rat plasma. The methods involved solid-phase extraction (SPE) using reverse adsorbents for separating the F-DNR and E-DNR, SPE using cation exchange adsorbents for separating the E-CYT, ultrafiltration for isolating the F-CYT and protein precipitation (PPT) for releasing the T-DNR and T-CYT totally from the liposomal forms. The analytes were subsequently quantified on ultra-high performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) individually with multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). The calibration curves showed good linear relationships over the concentration range of 0.22–44 μg/mL for E-DNR and T-DNR, 2–1000 ng/mL for F-DNR, 0.5–100 μg/mL for E-CYT and T-CYT, 4–2000 ng/mL for F-CYT respectively. For all the analytes, the within-and between-run precisions were less than13.6% and the accuracies (in terms of RE%) were within −12.5%. Besides, extraction recovery, matrix effect, dilution integrity and stability were also assessed. The methods were successfully applied to investigate the pharmacokinetics in Sprague–Dawley rats following i.v. administration liposomal formulation.

Quantification of Glucose, fructose and 1,5-Anhydroglucitol in plasma of diabetic patients by ultra performance liquid chromatography tandem mass spectrometry

Type 2 diabetes mellitus (T2DM), a worldwide disease that affects the quality of human life and social development. Glucose, fructose and 1,5-anhydroglucitol are closely related to diabetes mellitus. However, few methods have been reported to achieve these three carbohydrates in the blood simultaneously. In this study, a UPLC-MS/MS method allowing to quantify glucose, fructose, and 1,5-anhydroglucitol simultaneously in human plasma was developed. The analysis was performed by UPLC-MS/MS system with HILIC column. This new method provided satisfactory results in terms of calibration curves with good linearity (R2 > 0.99) over 3 order of magnitude range, precision (coefficient of variation of intra-day and inter-day: 0.72–10.23% and 2.21–13.8%), accuracy (results of intra-day and inter-day: 97–113%, 100–107%), matrix effects (87–109%), recovery (93–119%), carry-over (0.004–0.014%), as well as stability (0.04–6.9%) within the acceptance criteria. The reproducible, precise and accurate method with suitable dynamic ranges was successfully applied to the analysis of glucose, fructose and 1,5-anhydroglucitol in T2DM under different pathophysiological conditions.

The relationship between serum vitamin K concentration and coronary artery calcification in middle-aged and elderly people

BackgroundVitamin K is involved in the formation of coronary artery calcification which is an independent predictor of coronary heart disease. This study aims to explore the association between coronary artery calcification score and serum concentrations of vitamin K1, menaquinone-4 (MK-4) and menaquinone-7 (MK-7) in middle-aged and elderly Chinese population. MethodsA total of 116 patients who underwent CT coronary angiography were consecutively enrolled. Serum concentrations of vitamin K1, MK-4 and MK-7 were determined by high performance liquid chromatography tandem mass spectrometry. The relationships between coronary artery calcification score and serum vitamin K concentrations were analyzed. ResultsSignificantly lower serum vitamin K1 concentration was found in the patients with CACS > 400, comparing with the other CACS categories, respectively. Log (CACS + 1) was significantly higher in MK-4 < 0.05 ng/ml group compared with MK-4 ≥ 0.05 ng/ml group [2.03(0.21, 2.58) vs 1.31(0.00, 2.19), P < 0.05]. In subjects with established coronary calcification (defined as CACS > 10), vitamin K1 was found to be an independent factor contributing to higher CACS (r = −0.288, P = 0.013). ConclusionsIn this retrospective analysis, serum vitamin K1 and MK-4 concentrations were significantly lower in middle-aged and elderly cohorts with increasing calcification scores. The significant effect of vitamin K1 on CACS was only found in individuals who already had calcification. Whether the detection of circulating vitamin K in patients with preexisting coronary calcification could guide vitamin K supplementation needs further exploration.