spiked plasma
Recently Published Documents


TOTAL DOCUMENTS

73
(FIVE YEARS 26)

H-INDEX

13
(FIVE YEARS 3)

2021 ◽  
pp. 174751982110664
Author(s):  
Jue Chen ◽  
Tengmei Gao ◽  
Yinxia Chang ◽  
Yanming Wei ◽  
Yonghui Wang

Folate (FA) plays a key role in the biosynthesis of amino acids, purines, and pyrimidines in the human body, and intracellular folate metabolism has become an attractive target of tumor chemotherapy. In this work, an inclusion interaction was found between FA and cucurbit[7]uril (CB[7]), and the formation of a CB[7]-FA 2:1 supramolecular inclusion complex was confirmed by fluorescence spectra, UV-Vis absorption spectroscopy, 1H NMR, and molecular modeling calculations. In addition, FA is generally determined through the indirect fluorescent method because it shows weak fluorescence in aqueous solution. Therefore, a simple, direct fluorescence probe method for rapidly measuring FA was investigated, and the linear equation of FA was ΔF = 14.691C + 37.366 within the concentration ranges of 0.82 ~ 18.31 µg mL–1. The proposed direct fluorescence method was applied to the determination of spiked plasma. We demonstrated that this method could provide an experimental basis for the targeted administration of the CB[7]-FA complex, and it could be extended as a promising fluorescence detection method for drugs in vivo.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12516
Author(s):  
Sherry Cox ◽  
Lainey Harvill ◽  
Sarah Singleton ◽  
Joan B. Bergman ◽  
Becky DeBolt

Background The pharmacokinetics of ponazuril have been determined in several species; however, there is very little information on the stability of the drug after storage for long periods of time. This study was undertaken to determine the stability of ponazuril in plasma samples stored at −80 °C, which is the temperature most commonly used in the author’s laboratory. Method Spiked plasma samples (0.3, 7.5, and 15 µg/mL) were stored at −80 °C for three months. Analysis occurred on the first day and then once a week for the following twelve weeks. The drug was extracted using a chloroform extraction and separated by high performance liquid chromatography using ultraviolet detection. Results There was no loss of drug for any concentration for the first four weeks of storage. There was an average loss of less than 5% from day 35 through day 70 and an average loss of 6% on day 77 and 84. The data suggest that ponazuril is stable for 4 weeks when stored at −80 °C and undergoes minimal loss in the remaining 8 weeks.


2021 ◽  
Vol 20 (9) ◽  
pp. 1949-1959
Author(s):  
Mirina Sakhi ◽  
Abad Khan ◽  
Ismail Khan ◽  
Zafar Iqbal ◽  
Sumaira Irum Khan ◽  
...  

Purpose: To develop a simple, novel, sensitive and rapid reverse phase high performance liquid chromatographic method for simultaneous determination of paclitaxel, sorafenib and omeprazole in standard solutions and spiked human plasma and its application to the in-vitro and in-vivo evaluation of paclitaxel polymeric nanoparticle formulations.Methods: The method was tested for the assessment of paclitaxel, omeprazole and sorafenib using tamoxifen citrate as internal standard. The analysis was performed at a wavelength of 235 nm using Thermo HS C18 column, 40 °C column oven temperature, acetonitrile and water (70:30 v/v, pH 3.37 adjusted with phosphoric acid) as a mobile phase and at a flow rate of 0.8 ml/min. All analytes were extracted by simple protein precipitation method using acetonitrile. The linearity was assessed in the concentration range of 1 - 2000 ng/mL for paclitaxel, omeprazole and sorafenib.Results: The developed chromatographic method effectively separated omeprazole, paclitaxel, sorafenib and IS with retention time of 3.93, 5.18, 6.43 and 9.93 min, respectively. The chromatograms of the three target compounds and IS showed good resolution and peak separation. The LOD of the method was 1, 5 and. 5 ng/mL while the LOQ was 2, 7.5 and 10 ng/mL, for paclitaxel, sorafenib and omeprazole, respectively.Conclusion: The proposed RP-HPLC–UV method for the assessment of paclitaxel, sorafenib and omeprazole in standard solutions and spiked plasma is simple, economical, sensitive and robust. The method is also suitable for the analysis of paclitaxel in nanoformulations and for its pharmacokinetic studies in an animal model.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3190-3190
Author(s):  
Koichiro Yoneyama ◽  
Kazuo Tokuda ◽  
Tetsuhiro Soeda ◽  
Tomohisa Saito ◽  
Midori Shima

Abstract INTRODUCTION: Emicizumab is a bispecific antibody that mimics the cofactor function of activated factor VIII (FVIIIa) and is currently indicated for routine prophylaxis of bleeds in patients with congenital hemophilia A (PwCHA) regardless of factor VIII (FVIII) inhibitor status. Given its mechanism of action, the treatment response of emicizumab is expected to be similar between PwCHA and patients with acquired hemophilia A (AHA; PwAHA). However, it has not been well evidenced. We aimed to address this question by elucidating whether a healthy volunteer (HV)-derived, FVIII-neutralized, AHA-mimetic plasma produces similar pharmacodynamic (PD) responses of emicizumab to those in PwCHA. METHODS: In the phase I-I/II studies of emicizumab (Blood 2016;127:1633-41; N Engl J Med 2016;374:2044-53; Blood Adv 2017;1:1891-9; Haemophilia 2021;27:81-9), 40 Japanese HVs, 24 Caucasian HVs, 11 Japanese PwCHA with inhibitors (PwCHAwI), and 7 Japanese PwCHA without inhibitors (PwCHAwoI) were enrolled to receive emicizumab or placebo. These studies were conducted in accordance with relevant ethical standards as previously reported. Plasma samples were collected before first administration of the study drug, and they were spiked with emicizumab at 0, 0.3, 3, 30, or 300 μg/mL for HVs or 0, 3, or 300 μg/mL for PwCHA in combination with two anti-FVIII neutralizing antibodies (VIII-2236, anti-A2 type 1 inhibitor; VIII-9222, anti-C2 type 2 inhibitor) at approximately 300 μg/mL each (termed "ex vivo spiked plasma") for the measurement of activated partial thromboplastin time (APTT) and activated factor XI-triggered thrombin generation (TG). Separate plasma samples were collected before and after first administration (termed "in vivo exposed plasma") to be used for measuring APTT and TG, with ex vivo FVIII neutralization for HVs or without for PwCHA, as well as emicizumab concentration. Due to the difference in the given dosing regimens, observed plasma emicizumab concentrations did not largely overlap between HVs and PwCHA (up to 5.92 μg/mL as mean maximum concentration in HVs versus 10.3 to 120 μg/mL as mean steady-state trough concentration in PwCHA), which precluded simple comparison of the concentration-response (C-R) relationships between HVs and PwCHA in the in vivo exposed plasma. To overcome this limitation, nonlinear mixed-effect ("population") modeling was performed to analyze the C-R data from the ex vivo spiked plasma from HVs for APTT and TG each, and the developed population PD (PopPD) models were used to simulate C-R relationships in HVs over a wide range of plasma emicizumab concentration for comparison with those observed in the in vivo exposed plasma from PwCHA. RESULTS: In the ex vivo spiked plasma, the observed C-R relationships of APTT and TG were similar among Japanese HVs, Caucasian HVs, Japanese PwCHAwI, and Japanese PwCHAwoI, indicating similar FVIIIa-mimetic activity of emicizumab between HVs and PwCHA under the artificial FVIII-depleted condition ex vivo. The developed PopPD models adequately described the C-R data from HVs which were used for the model development. In the in vivo exposed plasma (Figure), the observed C-R relationships of APTT and TG were similar between Japanese HVs and Caucasian HVs as well as between Japanese PwCHAwI and Japanese PwCHAwoI. The observed C-R relationships in HVs were well captured by the PopPD model-based simulations despite these data being not directly used for the model development, which demonstrated the ability of the ex vivo data to be extrapolated in vivo. The PopPD models also well captured the observed C-R relationships in PwCHA, suggesting similar FVIIIa-mimetic activity of emicizumab between HVs and PwCHA in vivo. Some deviating observations from the PopPD model-based simulations might be attributed to the residual activity of given coagulation factor products, e.g., relatively short APTT and promoted TG at a plasma emicizumab concentration of 0 μg/mL (before first administration) in PwCHAwoI prior treated with FVIII prophylaxis. CONCLUSIONS: A HV-derived, FVIII-neutralized, AHA-mimetic plasma produced similar PD responses of emicizumab to those in PwCHA with or without inhibitors. Given its potential nature of mimicking AHA, i.e., coexistence of FVIII and multiple inhibitors including a type 2 one, the findings derived using this plasma may suggest similarity in the treatment response of emicizumab between PwCHA and PwAHA. Figure 1 Figure 1. Disclosures Yoneyama: Chugai Pharmaceutical Co., Ltd.: Current Employment, Patents & Royalties: Inventor of patents related to anti-FIXa/FX bispecific antibodies. Tokuda: Chugai Pharmaceutical Co., Ltd.: Current Employment. Soeda: Chugai Pharmaceutical Co., Ltd.: Current Employment, Patents & Royalties: Inventor of patents related to anti-FIXa/FX bispecific antibodies. Saito: Chugai Pharmaceutical Co., Ltd.: Current Employment. Shima: BioMarin Pharmaceutical Inc.: Membership on an entity's Board of Directors or advisory committees; Bayer AG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk A/S: Honoraria, Speakers Bureau; Takeda: Research Funding; CSL Behring: Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co., Ltd.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Inventor of patents related to anti-FIXa/FX bispecific antibodies, Research Funding, Speakers Bureau; Sanofi S.A.: Speakers Bureau; Fujimoto Seiyaku: Consultancy, Speakers Bureau. OffLabel Disclosure: Emicizumab for acquired hemophilia A


Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1110
Author(s):  
Qinglai Meng ◽  
Yao Wang ◽  
Yali Long ◽  
Aiping Yue ◽  
Michael Mecklenburg ◽  
...  

Currently, assays for rapid therapeutic drug monitoring (TDM) of β-lactam antibiotics in blood, which might be of benefit in optimizing doses for treatment of critically ill patients, remain challenging. Previously, we developed an assay for determining the penicillin-class antibiotics in blood using a thermometric penicillinase biosensor. The assay eliminates sample pretreatment, which makes it possible to perform semicontinuous penicillin determinations in blood. However, penicillinase has a narrow substrate specificity, which makes it unsuitable for detecting other classes of β-lactam antibiotics, such as cephalosporins and carbapenems. In order to assay these classes of clinically useful antibiotics, a novel biosensor was developed using New Delhi metallo-β-lactamase-1 (NDM-1) as the biological recognition layer. NDM-1 has a broad specificity range and is capable of hydrolyzing all classes of β-lactam antibiotics in high efficacy with the exception of monobactams. In this study, we demonstrated that the NDM-1 biosensor was able to quantify multiple classes of β-lactam antibiotics in blood plasma at concentrations ranging from 6.25 mg/L or 12.5 mg/L to 200 mg/L, which covered the therapeutic concentration windows of the tested antibiotics used to treat critically ill patients. The detection of ceftazidime and meropenem was not affected by the presence of the β-lactamase inhibitors avibactam and vaborbactam, respectively. Furthermore, both free and protein-bound β-lactams present in the antibiotic-spiked plasma samples were detected by the NDM-1 biosensor. These results indicated that the NDM-1 biosensor is a promising technique for rapid TDM of total β-lactam antibiotics present in the blood of critically ill patients.


2021 ◽  
Vol 21 (5) ◽  
pp. 1180
Author(s):  
Sekar Ayu Pawestri ◽  
Akhmad Kharis Nugroho ◽  
Endang Lukitaningsih ◽  
Purwantiningsih Purwantiningsih

Pharmacokinetics studies of domperidone generally analyze plasma matrix samples. The present work aimed to develop and validate a rapid and simple reversed phase-HPLC method for quantifying domperidone in plasma matrices. The chromatographic method implemented: 1. Luna Phenomenex® C18 (250 mm × 4.6 mm i.d; 5 µm) column, 2. isocratic mobile phase mixture of phosphate buffer 0.02 M:acetonitrile (70:30, v/v) with a flow rate of 1 mL/min, 3. UV detection at 285 nm. Domperidone and propranolol hydrochloride (as internal standard) were extracted from the deproteinated plasma sample. The method linearity was 0.998 in the range concentration of 15–200 ng/mL. The percentage of accuracy error was between -8.49–4.31%, while the percentage coefficient variation of precision ranged between 5.11–14.24%. This proposed method was simple, rapid (separation time less than 10 min), and selective. The validation parameters responses satisfied the method's requirements to determine domperidone in a plasma sample.


Author(s):  
Mohamed M.A. Hamdy ◽  
Mona M. Abdel Moneim

AbstractTramadol, a strong pain killer known for its addictive problems is either co-administrated or co-formulated with other analgesics or muscle relaxants. The power of fluorescence detection in HPLC is tested to resolve such mixtures in plasma matrix to reach the required sensitivity with simple sample treatment using just protein precipitation. The aim of this work was to develop an eco-friendly and sensitive HPLC method with fluorimetric detection for analysis of Tramadol in its two binary mixtures with Ibuprofen (mixture 1) and Chlorzoxazone (mixture 2) in two combined dosage forms and spiked plasma. Separation was done using a C18 column with mobile phase of acetonitrile and water (pH 3.5) in gradient elution and 1 mL/min flow rate. Detection was carried out with λ excitation/λ emission of 220 and 307 nm, respectively. The method was applied to detect the two binary mixtures in real plasma samples after invivo application to rats, to assure that the drugs’ metabolites do not affect the sensitivity or selectivity of the assay. Evaluation of greenness of the proposed method was done using semi-quantitative Eco‐Scale and new Green Analytical Procedure Index which showed that this method can be a greener alternative with higher sensitivity for analysis of both mixtures. The method (15 min-assay) was linear over concentrations of 0.1–10 μg/mL and 0.1–33 μg/mL in plasma. In addition, the proposed method was validated per ICH as well as FDA bioanalytical methods’ validation guidelines.


2020 ◽  
Vol 40 (S 01) ◽  
pp. S15-S20
Author(s):  
Jens Müller ◽  
Georg Goldmann ◽  
Natascha Marquardt ◽  
Bernd Pötzsch ◽  
Johannes Oldenburg

AbstractDue to structural differences between extended half-life (EHL) factor VIII (FVIII) or FIX products and equivalent plasma wild-type molecules used for assay calibration, reagent-dependent discrepancies during monitoring of FVIII- and FIX-replacement therapies with EHL products have been described. To assess the performance of available one-stage clotting and chromogenic substrate assays on the Siemens Atellica COAG 360 analyzer, an in vitro study using spiked plasma samples was performed. The described results confirm previously described findings and allowed allocation of each EHL product to an appropriate assay. In addition, corresponding EHL product–specific analytes were defined within the order entry system of the University Hospital Bonn. The requirement of product-specific FVIII and FIX assays complicates patient monitoring and demonstrates the need for both continuous education and communication between treating physicians and the coagulation laboratory.


Author(s):  
E Wallenburg ◽  
R J Brüggemann ◽  
K Asouit ◽  
M Teulen ◽  
A F J de Haan ◽  
...  

Abstract Objectives International quality control (proficiency testing) programmes are instituted to safeguard the analytical performance of laboratories and to aid these laboratories in identifying sources of error in their analytical methods. We describe the first international quality control programme for antimicrobial agents that are frequently used in critically ill patients. Methods Spiked plasma samples with ceftazidime, ciprofloxacin, flucloxacillin, piperacillin, sulfamethoxazole, N-acetyl sulfamethoxazole and trimethoprim were shipped to 22 laboratories from eight different countries. Acceptable accuracy by the performing laboratory was defined if measurements were within 80%–120% limits of the true weighed-in concentrations. Results A total of 81% of the measurements (ranging between 56% and 100%, dependent on drug) were within the 80%–120% limits of the true weighed-in concentrations. Conclusions We found a relatively good performance of the participating laboratories in measuring eight different antimicrobial drugs. Nevertheless, some of the antimicrobial drugs were not measured properly as up to 44% of the measurements was inaccurate depending on the drug. Our results emphasize the need for and utility of an ongoing quality control programme.


PLoS ONE ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. e0238954
Author(s):  
Huma Rao ◽  
Saeed Ahmad ◽  
Asadullah Madni ◽  
Imtiaz Ahmad ◽  
Muhammad Nadeem Shahzad

Sign in / Sign up

Export Citation Format

Share Document