scholarly journals UHPLC-MS/MS Analysis of Cannabidiol and Its Metabolites in Serum of Patients with Resistant Epilepsy Treated with CBD Formulations

2021 ◽  
Vol 14 (7) ◽  
pp. 630
Author(s):  
Sara Malaca ◽  
Massimo Gottardi ◽  
Federica Pigliasco ◽  
Sebastiano Barco ◽  
Alessia Cafaro ◽  
...  
Keyword(s):  
High Performance ◽  
Serum Levels ◽  
European Medicines Agency ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Childhood Onset ◽  
Serum Samples ◽  
First Time ◽  
The Relationship ◽  
Promising Therapeutic Agent

Cannabidiol (CBD) is a promising therapeutic agent with analgesic, myorelaxant, and anti-epileptic actions. Recently, a purified form of CBD (Epidiolex®) has been approved by the European Medicines Agency (EMA) for the treatment of two highly-refractory childhood-onset epilepsies (Dravet and Lennox-Gastaut syndrome). Given the interindividual response and the relationship between the dose administered and CBD blood levels, therapeutic drug monitoring (TDM) is a valuable support in the clinical management of patients. We herein report for the first time a newly developed and validated method using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) to evaluate CBD and its metabolites (i.e., cannabidiol-7-oic acid (7-COOH-CBD), 7-hydroxycannabidiol (7-OH-CBD), 6-α-hydroxycannabidiol (6-α–OH–CBD) and 6-β-hydroxycannabidiol (6-β–OH–CBD)) in serum samples. The method reached the sensitivity needed to detect minimal amounts of analytes under investigation with limits of quantification ranging from 0.5 to 20 ng/mL. The validation results indicated in this method were accurate (average inter/intra-day error, <15%), precise (inter/intra-day imprecision, <15%), and fast (8 min run time). The method resulted to be linear in the range of 1–10,000 ng/mL for CBD-COOH, 1–500 ng/mL for 7-OH-CBD and CBD and 1–25 ng/mL for 6-α–OH–CBD and 6-β–OH–CBD. Serum levels of CBD (88.20–396.31 and 13.19–170.63 ng/mL) as well as of 7-OH-CBD (27.11–313.63 and 14.01–77.52 ng/mL) and 7-COOH-CBD (380.32–10,112.23 and 300.57–2851.82 ng/mL) were significantly higher (p < 0.05) in patients treated with GW pharma CBD compared to those of patients treated with galenic preparations. 6-α–OH–CBD and 6-β–OH–CBD were detected in the first group and were undetectable in the second group. 7-COOH-CBD was confirmed as the most abundant metabolite in serum (5–10 fold higher than CBD) followed by 7-OH-CBD. A significant correlation (p < 0.05) between the dose administrated and a higher bioavailability was confirmed in patients treated with a GW pharma CBD preparation.

Personalized antibiotic therapy – a rapid high performance liquid chromatography–tandem mass spectrometry method for the quantitation of eight antibiotics and voriconazole for patients in the intensive care unit

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tony Böhle ◽  
Ulrike Georgi ◽  
Dewi Fôn Hughes ◽  
Oliver Hauser ◽  
Gudrun Stamminger ◽  
...  
Keyword(s):  
Intensive Care ◽  
Antibiotic Therapy ◽  
High Performance ◽  
High Specificity ◽  
Serum Levels ◽  
Turnaround Time ◽  
Target Range ◽  
Therapeutic Drug ◽  
Monitoring Method ◽  
Adjustment Procedure

AbstractObjectivesFor a long time, the therapeutic drug monitoring of anti-infectives (ATDM) was recommended only to avoid the toxic side effects of overdosing. During the last decade, however, this attitude has undergone a significant change. Insufficient antibiotic therapy may promote the occurrence of drug resistance; therefore, the “one-dose-fits-all” principle can no longer be classified as up to date. Patients in intensive care units (ICU), in particular, can benefit from individualized antibiotic therapies.MethodsPresented here is a rapid and sufficient LC-MS/MS based assay for the analysis of eight antibiotics (ampicillin, cefepime, cefotaxime, ceftazidime, cefuroxime, linezolid, meropenem, and piperacillin) applicated by continuous infusion and voriconazole. In addition a dose adjustment procedure for individualized antibiotic therapy has been established.ResultsThe suggested dose adjustments following the initial dosing of 121 patient samples from ICUs, were evaluated over a period of three months. Only a minor percentage of the serum levels were found to be within the target range while overdosing was often observed for β-lactam antibiotics, and linezolid tended to be often underused. The results demonstrate an appreciable potential for β-lactam savings while enabling optimal therapy.ConclusionsThe presented monitoring method provides high specificity and is very robust against various interferences. A fast and straightforward method, the developed routine ensures rapid turnaround time. Its application has been well received by participating ICUs and has led to an expanding number of hospital wards participating in ATDM.

Therapeutic drug monitoring of adalimumab in RA: no predictive value of adalimumab serum levels and anti-adalimumab antibodies for prediction of response to the next bDMARD

2020 ◽  
Vol 79 (7) ◽  
pp. 867-873
Author(s):  
Evy Ulijn ◽  
Nathan den Broeder ◽  
Maike Wientjes ◽  
Noortje van Herwaarden ◽  
Inger Meek ◽  
...  
Keyword(s):  
Predictive Value ◽  
Evidence Synthesis ◽  
Serum Levels ◽  
Subsequent Treatment ◽  
Therapeutic Drug ◽  
Test Accuracy ◽  
Serum Samples ◽  
Best Evidence Synthesis ◽  
Adalimumab Treatment ◽  
Sensitivity Specificity

BackgroundAfter adalimumab treatment failure, tumour necrosis factor inhibition (TNFi) and non-TNFi biological disease-modifying anti-rheumatic drugs (bDMARDs) are equally viable options on a group level as subsequent treatment in rheumatoid arthritis (RA) based on the current best evidence synthesis. However, preliminary data suggest that anti-adalimumab antibodies (anti-drug antibodies, ADA) and adalimumab serum levels (ADL) during treatment predict response to a TNFi as subsequent treatment.ObjectiveTo validate the association of presence of ADA and/or low ADL with response to a subsequent TNFi bDMARD or non-TNFi bDMARD. Sub-analyses were performed for primary and secondary non-responders.MethodsA diagnostic test accuracy retrospective cohort study was done in consenting RA patients who discontinued adalimumab after >3 months of treatment due to inefficacy and started another bDMARD. Inclusion criteria included the availability of (random timed) serum samples between ≥8 weeks after start and ≤2 weeks after discontinuation of adalimumab, and clinical outcome measurements Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) between 3 to 6 months after treatment switch. Test characteristics for EULAR (European League Against Rheumatism) good response (DAS28-CRP based) after treatment with the next (non-)TNFi bDMARD were assessed using area under the receiver operating characteristic and sensitivity/specificity.Results137 patients were included. ADA presence was not predictive for response in switchers to a TNFi (sensitivity/specificity 18%/75%) or a non-TNFi (sensitivity/specificity 33%/70%). The same was true for ADL levels in patients that switched to a TNFi (sensitivity/specificity 50%/52%) and patients that switched to a non-TNFi (sensitivity/specificity 32%/69%). Predictive value of ADA and ADL were similar for both primary and secondary non-responders to adalimumab.ConclusionsIn contrast to earlier research, we could not find predictive value for response to a second TNFi or non-TNFi for either ADA or random timed ADL.

Numbers of Natural Teeth, Diet, and Nutritional Status in US Adults

2007 ◽  
Vol 86 (12) ◽  
pp. 1171-1175 ◽  
Author(s):  
R.E. Nowjack-Raymer ◽  
A. Sheiham
Keyword(s):  
Vitamin C ◽  
Nutritional Status ◽  
High Performance ◽  
Beta Carotene ◽  
Serum Levels ◽  
Dental Status ◽  
Multilinear Regression ◽  
Dietary Recall ◽  
Natural Teeth ◽  
The Relationship

Evidence that dental status affects diet is equivocal. The hypothesis of this study was that diet was affected by dental status. The objective was to assess the relationship between numbers of teeth and diet and nutritional status in US adult civilians without prostheses. We examined 6985 NHANES (1988–1994) participants. Data included socio-economics, demographics, dental status, and diet and nutritional status. Dietary data were obtained from food frequency questionnaires and 24-hour dietary recall. Serum levels of beta carotene, folate, and vitamin C were measured with isocratic high-performance liquid chromatography. The population was classified by numbers of teeth. Covariance and Satterthwaite F-adjusted statistical comparisons were made between tooth groupings and the fully dentate population. Multilinear regression models adjusted for covariates. People with fewer than 28 teeth had significantly lower intakes of carrots, tossed salads, and dietary fiber than did fully dentate people, and lower serum levels for beta carotene, folate, and vitamin C. Dental status significantly affects diet and nutrition.

scholarly journals Bioanalytical Method Optimization for the Therapeutic Drug Monitoring of Vancomycin

2017 ◽  
Vol 2 (2) ◽  
pp. 89-95
Author(s):  
Maria Mercedes De Zan
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
High Performance ◽  
European Medicines Agency ◽  
Therapeutic Drug ◽  
Core Shell ◽  
Sample Treatment ◽  
Method Optimization ◽  
Shell Particles

Chemometric optimization and validation of a method based on High Performance Liquid Chromatography (HPLC) using core – shell particles for the determination of Vancomycin (VMC) in human plasma is reported. The combination of the efficiency of the core-shell particles and the benefits of the design of experiments allowed the successful determination of VCM, even in presence of several interferents. Selectivity, linearity, accuracy and precision were accomplished according to the European Medicines Agency (EMA) guideline, within the concentration range of 1.00 – 60.0 μg/mL of VCM. It is noteworthy that this method requires small amount of sample and solvents, and the sample treatment is simple and no time-consuming. Thus, this method becomes a simple and high-throughput alternative to therapeutic drug monitoring in treated patients, as well as an analytical procedure that conforms to the principles of the green chemistry.

scholarly journals The Pharmacokinetic Study of Progesterone and Allopregnanolone in Refractory Epilepsy : Phase II Study

2021 ◽  
Author(s):  
Marisa Senngam ◽  
Juthathip Suphanklang ◽  
Wichai santimaleeworagun ◽  
Piradee Suwanpakdee ◽  
Pornsawan Mekhasingharrak ◽  
...  
Keyword(s):  
Seizure Frequency ◽  
Maximum Concentration ◽  
Refractory Epilepsy ◽  
Serum Levels ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Serum Progesterone ◽  
Minimum Concentration ◽  
Clinical Trials Registry ◽  
The Relationship

Abstract Background: Progesterone belongs to a class of neurosteroids used for the reduction of seizure frequency in patients with refractory epilepsy. However, the pharmacokinetics of progesterone and its active derivative, allopregnanolone, have never been studied in these patients. Objectives: This study was aim to explore the pharmacokinetic parameters of progesterone 400 mg every 12 h, for 3 months, in patients with refractory epilepsy as an add-on therapy to control seizures. Phoenix® WinNonlin® was used to analyse the pharmacokinetic parameters. Results: Twelve patients were recruited. From a therapeutic drug monitoring, the serum progesterone and allopregnanolone levels after taking the first dose of progesterone were characterised by a time to maximum concentration (Tmax) median of 1 and 2.5 h, a maximum concentration (Cmax) median of 274.97 and 3.81 ng/mL, and a minimum concentration (Cmin) median of 56.93 and 1.06 ng/mL, respectively. The median values of the pharmacokinetic parameters of progesterone and allopregnanolone during the steady state were as follows: t1/2 of 2.4 and 2.0 h, Cmax of 964.35 and 8.92 ng/mL, and Cmin of 64.67 and 1.86 ng/mL, respectively. By examining the relationship between the progesterone or allopregnanolone concentrations with seizure-controlling ability, we could identify a responder patient group with 6- to 7-fold higher serum concentrations of progesterone and allopregnanolone than the non-responders. Conclusions: We could establish higher serum levels of both progesterone and allopregnanolone, which could consequently relate to lowering the seizure frequency in patients with refractory epilepsy. The suggested progesterone dose was 400 mg orally every 12 h against refractory epilepsy Trial registration: This study has been registered on the Thai Clinical Trials Registry (No. TCTR20200710005, 10 July 2020)

scholarly journals Environmental Pollution to Blame for Depressive Disorder?

2021 ◽  
Author(s):  
Mariana Segovia-Mendoza ◽  
Margarita Isabel Palacios-Arreola ◽  
Lenin Pavón ◽  
Enrique Becerril ◽  
Karen Elizabeth Nava-Castro ◽  
...  
Keyword(s):  
Depressive Disorder ◽  
Neurological Disorders ◽  
Serum Levels ◽  
Blood Levels ◽  
Public Concern ◽  
Bisphenol S ◽  
Major Depressive ◽  
Clinical Associations ◽  
Butyl Phthalate ◽  
First Time

Public concern has emerged about the effects of endocrine disruptor compounds (EDCs) on neuropsychiatric disorders. Preclinical evidence suggests that exposure to EDCs is associated with the development of the major depressive disorder (MDD) and could result in neural degeneration. The interaction of EDCs with hormonal receptors is the best-described mechanism of their biological activity. However, the dysregulation of the hypothalamic-pituitary-gonadal adrenal axis has been reported and linked to neurological disorders. On the other hand, at a worldwide level and in Mexico, the incidence of MDD has recently been increasing. Of note, in Mexico, there are no clinical associations on blood levels of EDCs and the incidence of the MDD. Methodology: Thus, we quantified for the first time the serum levels of parent compounds of two bisphenols and four phthalates in patients with MDD. Results: The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP), and di-ethyl-phthalate (DEP), bisphenol A (BPA), and bisphenol S (BPS) were determined with a gas chromatograph-mass spectrometer. Results/ conclusion: We found significant differences between concentrations of BBP between controls and patients with MDD.

Field deployable platform for prognostic hepatic cancer screening.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 267-267
Author(s):  
Jill E. Shea ◽  
Jennifer H Granger ◽  
Mark D Porter ◽  
Courtney L. Scaife
Keyword(s):  
High Risk ◽  
Point Of Care ◽  
Low Cost ◽  
Serum Levels ◽  
Blood Levels ◽  
Vertical Flow ◽  
Serum Samples ◽  
Point Of Care System ◽  
Risk Patients ◽  
Care System

267 Background: Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world particularly in low- and middle-income countries (LMICs). Although treatable if identified in the early stages in many LMICs patients are identified later in disease. A low cost point of care system that could identify patients at a higher risk of having HCC could be used as a screening tool to identify patients at an earlier stage. We are currently developing a low cost point of care hand held platform that can simultaneously evaluate the blood levels of common HCC markers. We present our preliminary findings on the limit of detection (LOD) of our system. Methods: Our device combines the rapid but qualitative results of a vertical flow assay with the quantitative capabilities of surface enhanced Raman scattering spectroscopy. Our final product will be able to simultaneously measure the blood levels of the five most proven markers of HCC: alphafetoprotein (AFP), lens-culinaris agglutinin binding alphafetoprotein (AFP-L3), des-gamma-carboxy prothrombin (DCP), core antibodies to hepatitis B virus (HBV), and core antibodies to hepatitis C virus (HCV). In this pilot study we initially evaluated the LOD of our system by evaluating known concentrations of AFP in human serum samples. We then evaluated serum levels of AFP in HCC patient samples (n = 5) with our device and compared with values obtained using a standard ELISA. Results: The LOD of our system for the detection of AFP in spiked serum samples was 1 ng/mL. Our quantitative lateral flow assay measured AFP within 10% of the values of obtained by standard ELISA, with serum values ranging from 10-900 ng/mL. The quantitative vertical flow assay was able to provide results within 5 minutes at a cost of approximately $2/sample. Conclusions: Our inexpensive, portable and rapid test was able to measure serum levels of AFP at values comparable to standard clinical methods. Importantly, one blood marker would be insufficient to identify high risk patients, so further research will be required to expand the number of markers within the panel. The end goal will be to evaluate the ability of our point of care system to screen high risk population in LMICs, thereby identifying at risk patients earlier in disease progression.

Liquid chromatography and fluorescence polarization immunoassay methods compared for measuring flecainide acetate in serum.

1987 ◽  
Vol 33 (10) ◽  
pp. 1898-1900 ◽  
Author(s):  
R J Straka ◽  
T J Hoon ◽  
R L Lalonde ◽  
J A Pieper ◽  
M B Bottorff
Keyword(s):  
Liquid Chromatography ◽  
Fluorescence Polarization ◽  
High Performance ◽  
Therapeutic Drug ◽  
Fluorescence Polarization Immunoassay ◽  
Serum Samples ◽  
Coefficients Of Variation ◽  
Flecainide Acetate ◽  
Assay Methods ◽  
The Mean

Abstract We analyzed 99 patients' serum samples for concentrations of a new antiarrhythmic agent, flecainide acetate, by fluorescence polarization immunoassay (FPIA) and "high-performance" liquid chromatography (HPLC). Within-day and between-day coefficients of variation at concentrations in the low and high ends of the therapeutic range were less than 7% for HPLC and less than 9% for FPIA. There was no statistical difference in the mean (+/- SD) concentrations of the clinical serum samples measured by the two methods (607 +/- 334 micrograms/L by HPLC, 602 +/- 344 micrograms/L by FPIA), but results by each differed by a mean of 0.13%. FPIA and HPLC measurements correlated significantly (r = 0.98, P less than 0.05), and were linearly related (slope = 0.970, intercept = 13 micrograms/L) as assessed by orthogonal regression. Both assay methods produced similar concentration measurements and were sufficiently accurate and precise to be used in therapeutic drug monitoring.

Measurement of mycophenolic acid in plasma or serum by a commercial enzyme inhibition technique in comparison with a high performance liquid chromatography method

2008 ◽  
Vol 46 (9) ◽  
Author(s):  
Dustin R. Bunch ◽  
Sihe Wang
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Enzyme Inhibition ◽  
Mycophenolic Acid ◽  
High Performance ◽  
Random Access ◽  
Hplc Method ◽  
Clinical Samples ◽  
Therapeutic Drug ◽  
Serum Samples

Abstract: Mycophenolic acid (MPA) is the primary active metabolite of the immunosuppressant mycophenolate mofetil. High performance liquid chromatography (HPLC) is commonly used for therapeutic drug monitoring (TDM) of MPA but requires batched runs. Recently, an enzyme inhibition assay (EIA) was approved for MPA TDM on random-access platforms using either serum or EDTA plasma. We evaluated the EIA on a Roche Integra 400 using serum and heparinized plasma in comparison with a validated HPLC method.: Heparinized plasma from leftover clinical samples on which MPA was ordered along with paired serum samples, drawn at the same time for other clinical tests, were used for the method comparison.: The EIA was linear from 3.1 to 44.0 μmol/L with an accuracy of 93.9%–107.1%. The intra- and inter-day variations were 0.5%–2.7% and 1.6%–2.1%, respectively. The limit of detection was 0.8 μmol/L and the limit of quantification was 3.1 μmol/L. The method showed a mean bias of 0.6 μmol/L (7.6%) in serum samples (3.1–34.1 μmol/L) vs. the HPLC method using paired plasma (n=229). Heparinized plasma (n=114) vs. serum showed a mean bias of –0.1 μmol/L (–1.6%) by the EIA.: The random-access EIA on Integra 400 is acceptable for clinical MPA TDM in either serum or heparinized plasma.Clin Chem Lab Med 2008;46:1281–4.

scholarly journals Increased Serum Levels of Cadmium are Associated with an Elevated Risk of Cardiovascular Disease in Adults

2021 ◽  
Author(s):  
Siyu Ma ◽  
Jie Zhang ◽  
Cheng Xu ◽  
Min Da ◽  
Yang Xu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
White Blood Cells ◽  
Serum Levels ◽  
Blood Levels ◽  
C Reactive Protein ◽  
Epidemiological Evidence ◽  
Reactive Protein ◽  
Health And Nutrition ◽  
The Relationship ◽  
Inflammation Parameters

Abstract Previous studies have determined the effects of exposure to some heavy metals on cardiovascular disease (CVD); however, the association between exposure to cadmium and CVD in adults remains unclear. The relationship between serum levels of cadmium and the risk of CVD was studied by analysing available data from 38,223 participants who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. After adjusting for all covariates, we found that higher serum cadmium concentrations were positively related to both the overall risk of CVD (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.22, 1.72; p for trend <0.001) and the risks of its subtypes, including congestive heart failure, coronary heart disease, heart attack and stroke. Elevated levels of cadmium were associated with increased levels of lipids and inflammation parameters, including blood triglycerides, total cholesterol, white blood cells (WBCs) and C-reactive protein (CRP). Our study provided epidemiological evidence that cadmium may increase the risk of CVD by elevating blood lipids and inflammation. CapsuleHigh blood levels of Cd are associated with increased risks of overall CVD and four of the CVD subtypes

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