scholarly journals LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Lili Cui ◽  
Zhipeng Wang ◽  
Shi Qiu ◽  
Mengwei Zhang ◽  
Yanping Liu ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Half Life ◽  
Correlation Coefficients ◽  
Sample Pretreatment ◽  
Life Time ◽  
Gradient Elution ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Good Linearity ◽  
Ultrahigh Performance Liquid Chromatography

Hydroxychloroquine (HCQ) was originally used as an antimalarial and immunomodulation drug. We developed and validated a simple and sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantitation of HCQ and its three metabolites in rat blood, and reported their pharmacokinetic parameters. The chromatographic separation and detection of analytes were achieved within 4 min on ZORBAX SB-C8 (3.5 μm, 2.1 × 150 mm) column with gradient elution, and the flow rate was 0.25 mL/min. Simple protein precipitation was successfully applied for sample pretreatment. The HCQ displays a good linearity in the range of 2.0–5000.0 ng/mL, and the three metabolites also show good linearity ranging from 1.0 to 2500.0 ng/mL, with all correlation coefficients (R2) better than 0.98. In conclusion, this rapid, sensitive method was successfully developed, validated, and then applied to a pharmacokinetic study of HCQ in rat model in high dose. The results of the pharmacokinetic study presented an average half-life time 21.14 ± 10.31 h (mean ± SD) of HCQ, which is much shorter in human compared to that in mice. For the three metabolites, longer half-life times (approximately 100 h) were shown in rat.

scholarly journals Pharmacokinetics of PEGylated Recombinant Human Erythropoietin in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaohan Cao ◽  
Zhiyong Chen ◽  
Zhuoran Yu ◽  
Yonghong Ge ◽  
Xianyin Zeng
Keyword(s):  
Half Life ◽  
Life Time ◽  
Intramuscular Administration ◽  
Pharmacokinetic Parameters ◽  
Human Erythropoietin ◽  
Large Molecular Weight ◽  
Major Route ◽  
High Concentrations ◽  
Different Doses

rHuEPO plays a central role as chemicals for the treatment of many diseases. Due to its short half-life, the main aim for this pharmacokinetic study is to investigate a newly developed PEG-rHuEPO with large molecular weight in SD rats. After a single intramuscular administration of different doses of 125I-PEG-rHuEPO, pharmacokinetic parameters, tissue distribution, and excretion were analyzed. Inin vivohalf-life time measured after 125I-PEG-rHuEPO administration at the doses of 1, 2, and 3 μg/kg,t1/2αwas 1.90, 1.19, and 2.50 hours, respectively, whereast1/2βwas 22.37, 26.21, and 20.92 hours, respectively; at 8, 24, and 48 hours after intramuscular administration, PEG-rHuEPO was distributed to all of the examined tissues, however, with high concentrations of radioactivity, only in plasma, blood, muscle at the administration site, and bone marrow. Following a 2 μg/kg single intramuscular administration, approximately 21% of the radiolabeled dose was recovered after almost seven days of study. Urine was the major route of excretion; 20% of the administered dose was recovered in the urine, while excretion in the feces was less than 1.4%. Therefore, this PEG-rHuEPO has potential to be clinically used and could reduce frequency of injection.

scholarly journals Quantification and Confirmation of Zearalenone Using a LC-MS/MS QTRAP System in Multiple Reaction Monitoring and Enhanced Product Ion Scan Modes.

2020 ◽  
Author(s):  
Shencong lv ◽  
Xiaoqiong Wu ◽  
Guoying Zhu ◽  
Jian Guan ◽  
Yong Yan ◽  
...  
Keyword(s):  
Time Perspective ◽  
Ion Trap ◽  
Corn Oil ◽  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Correlation Coefficients ◽  
Sample Pretreatment ◽  
Gradient Elution ◽  
Reaction Monitoring ◽  
Liquid Chromatography Tandem Mass

Abstract Background: A simple, rapid, and efficient liquid chromatography tandem mass spectrometry (LC–MS/MS) method, operated in electrospray ionization (ESI) and quadrupole linear ion trap modes, has been developed for the identification and structural characterization of zearalenone (ZEN) in corn oil. Methods: Samples (5 g) were extracted with acetonitrile/water (80:20, v/v). After centrifugation and dilution, the extracts were separated on a C18 analytical column by gradient elution (acetonitrile/water) and analyzed by UPLC–MS/MS. Enhanced product ion mode was used for qualitative analysis, while multiple reaction monitoring mode was used for quantitative analysis. Results: Calibration curve showed good linearity with correlation coefficients (r) higher than 0.995. Limit of detection was determined to be below 0.20 μg kg-1 for ZEN. The recovery for ZEN was in the acceptable range of 86.6% to 97.2%. 82.4 % of the samples were found to contain ZEN among the 51 samples.Conclusion: The sample pretreatment and LC–MS methods developed in this research, from a convenience and analysis time perspective, are simple, efficient, cheaper, and less time-consuming than existing methods.

scholarly journals Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method

2021 ◽  
Vol 71 (3) ◽  
pp. 415-428
Author(s):  
Sai-Jie Zuo ◽  
Xiao-Liang Cheng ◽  
Dong-Zheng Liu ◽  
Wei-Yi Feng ◽  
Yong-Xiao Cao ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Growth Factor Receptor ◽  
Internal Standard ◽  
Gradient Elution ◽  
Storage Conditions ◽  
Rat Plasma ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Parameters ◽  
Egfr Inhibitor ◽  
Reliable Quantification

Abstract1-(4-(Pyrrolidin-1-yl-methyl)phenyl)-3-(4-((3-(trifluoromethyl) phenyl)amino)quinazolin-6-yl)urea (ZCJ14), a novel epidermal growth factor receptor (EGFR) inhibitor, with diarylurea moiety, displays anticancer effect. In the present study, an LCMS/MS method was established to determine the concentration of ZCJ14 in rat plasma. Furthermore, the method was applied to investigate the pharmacokinetic characteristics of ZCJ14. Chromatographic separation of ZCJ14 and internal standard (IS) [1-phenyl-3-(4-((3-(trifluoromethyl)phenyl)amino) quinazolin-6-yl)urea] was accomplished by gradient elution using the Kromasil C18 column. The selected reaction monitoring transitions were performed at m/z 507.24→436.18 and 424.13→330.96 for ZCJ14 and IS, resp. The established method was linear over the concentration range of 10–1000 ng mL−1. The intra- and inter-day precisions were < 11.0 % (except for LLOQ which was up to 14.3 %) and the respective accuracies were within the range of 87.5–99.0 %. The extraction recovery and matrix effect were within the range of 88.4–104.5 % and 87.3–109.9 %, resp. ZCJ14 was stable under all storage conditions. The validated method was successfully applied to the pharmacokinetic study of ZCJ14 in rats, and the pharmacokinetic parameters have been determined. The oral bioavailability of ZCJ14 was found to be 46.1 %. Overall, this accurate and reliable quantification method might be useful for other diarylurea moiety-containing drugs.

Pharmacokinetic Study of Cefazolin in Short Daily Hemodialysis

2018 ◽  
Vol 53 (4) ◽  
pp. 348-356
Author(s):  
Katie Palmer ◽  
Scott Walker ◽  
Robert Richardson ◽  
Sarbjit V. Jassal ◽  
Marisa Battistella
Keyword(s):  
Pharmacokinetic Study ◽  
Half Life ◽  
Total Serum ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Median Percentage ◽  
Daily Hemodialysis ◽  
Drug Concentrations ◽  
Initiation Of Dialysis ◽  
Short Daily Hemodialysis

Background: A number of centers across the world offer short daily hemodialysis (SDHD) treatments. To date, cefazolin pharmacokinetics have not been described in patients undergoing SDHD. Objective: The purpose of this study was to investigate the effect of SDHD on the pharmacokinetics of cefazolin. Methods: This was a prospective, open-label, pharmacokinetic study of cefazolin during SDHD in 10 noninfected patients. Participants received a 1-g intravenous (IV) infusion of cefazolin after SDHD on study day 1 and a second dose after SDHD on study day 2. To determine the concentration of cefazolin, 6 blood samples were drawn at 0, 1, 2, 2.3, 4, and 24 hours after initiation of dialysis on day 2, and 2 dialysate samples were drawn at 1 and 2 hours after initiation of dialysis on day 2. Samples were analyzed using high-performance liquid chromatography, and pharmacokinetic parameters were determined. Results: Median interdialysis clearance was 0.16 L/h (interquartile range [IQR]: 0.11-0.21 L/h), and median intradialysis clearance was 1.95 L/h (IQR: 1.66-2.45 L/h). Median interdialysis half-life was 28.2 hours (IQR: 23.5-59.3 hours) as compared with a median intradialysis half-life of 2.3 hours (IQR: 1.7-2.7 hours). The median percentage removal of cefazolin during dialysis was 41% (IQR: 35%-53%). Conclusion and Relevance: Estimated cefazolin dialysis clearance is similar to previous estimates with conventional thrice-weekly regimens. Current dosing recommendations of 1 g IV post-SDHD achieve total serum drug concentrations greater than 40 mg/L in all patients, which is the total drug concentration required for bactericidal activity against Staphylococcus species.

Efficacy of Individualized Preventive Treatment of Patients with Severe Hemophilia A Guided by Multiple Clinical Parameters and Pharmacokinetics

2021 ◽  
Author(s):  
Youqun Wang ◽  
Qiao Yang ◽  
Liangda Zheng ◽  
Xianting Wang ◽  
Wenhua Jiang ◽  
...  
Keyword(s):  
Half Life ◽  
Economic Benefit ◽  
Hemophilia A ◽  
Preventive Treatment ◽  
Life Time ◽  
Pharmacokinetic Parameters ◽  
Clinical Parameters ◽  
Severe Hemophilia ◽  
Blood Types ◽  
Before And After

Objective: To investigate the effect of multiple clinical parameters (age, weight, blood types, and bleeding types) on FⅧ pharmacokinetic parameters (PK parameters) in adult patients with severe hemophilia A (SHA), draw up individualized preventive treatment plans, and observe clinical efficacy and economic benefit. Methods: Forty SHA patients treated in our hospital from January 2018 to May 2019 were enrolled, with their age, weight, blood types, bleeding types, and PK parameters measured to analyze the effects of clinical parameters on PK parameters. Individualized preventive treatment was developed, and patients were followed up for 1 year. The annual bleeding times (ABR), annual joint bleeding times (AJBR), and annual FⅧ dosage were observed and compared before and after treatment. Results: Weight, blood types and bleeding types could affect the PK parameters of FVIII. A prevention plan was formulated under the guidance of FVIII half-life. After 1 year of follow-up, ABR decreased by 88.9%, AJBR decreased by 90%, and annual FⅧ dosage increased by 47%. The dosage of FⅧ in 8 patients after was less than that before prevention, and the average half-life time of these 8 patients was 13.32 h. Conclusions: 1. Weight, blood types, and bleeding types of adult SHA patients could affect FVIII half-life. As body mass index increased, FVIII half-life were significantly prolonged. The FVIII half-life of patients with type O blood were significantly shorter than those with other blood types, and the FVIII half-life of knee joint bleeding were conspicuously shorter than those of elbow joint bleeding. 2. Individualized preventive treatment could markedly reduce bleeding times. For patients with a long half-life period, the total annual FⅧ dosage could be reduced to achieve bleeding prevention and economic benefit.

scholarly journals Simultaneous Quantification of Pioglitazone and Omarigliptin in Rat Plasma by UHPLC-MS/MS and Its Application to Pharmacokinetic Study after Coadministration of the Two Drugs

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lin Wang ◽  
Jiaxi Wang ◽  
Chao Lin ◽  
Furong Wang ◽  
Xiangping Li ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Meta Analysis ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Ion Source ◽  
Pharmacokinetic Parameters ◽  
Column Temperature ◽  
Linear Relationships ◽  
Long Acting

Combination therapy is a common approach for clinical treatment of type 2 diabetes mellitus, especially for patients with poor monotherapy. Meta-analysis suggested that omarigliptin, a long-acting DPP-4 inhibitor, combined with pioglitazone might improve the side effects of pioglitazone. However, little is known about the pharmacokinetic properties after a coadministration. In this study, a rapid and reliable method for the simultaneous determination of the pioglitazone and omarigliptin in rat plasma by UHPLC-MS/MS was established and validated for the first time. An exsil mono C18 column (2.0 × 50 mm, 3 μm) was used to separate the analytes and the column temperature was kept at 30°C. Sitagliptin was selected as the internal standard. 0.02% formic acid aqueous solution (A) and methanol-acetonitrile (B) were used as mobile phases with gradient elution at a flow rate of 0.3 mL/min. The elution procedure was as follows: 20%B (0–0.1 min), 80%B (0.1–0.3 min), 80%B (0.3–2.0 min), and 20%B (2.1–3.0 min). A multiple reaction monitor (MRM) was used under positive ionization mode with electrospray ion source to detect pioglitazone (357.1 ⟶ 134.1), omarigliptin (399.2 ⟶ 153.0), and sitagliptin (408.2 ⟶ 235.0). The linear ranges of pioglitazone and omarigliptin were 5–2000 ng/mL and 10–4000 ng/mL, respectively. Good linear relationships were exhibited in the corresponding linear ranges (r ≥ 0.9944). The bioanalytical method was validated, and the selectivity, linearity, sensitivity, accuracy, precision, stability, recovery, and matrix effect were acceptable. The validated method was then successfully applied to pharmacokinetic study of pioglitazone combined with omarigliptin in rats. Results suggested that the combination of the two drugs had little effect on the pharmacokinetic parameters of each other in rats.

Pharmacokinetics of propofol in rainbow trout following bath exposure

2015 ◽  
Vol 18 (1) ◽  
pp. 147-152 ◽  
Author(s):  
P. Gomułka ◽  
E. Fornal ◽  
B. Berecka ◽  
A. Szmagara ◽  
E. Ziomek
Keyword(s):  
Rainbow Trout ◽  
Plasma Concentration ◽  
Oncorhynchus Mykiss ◽  
Blood Plasma ◽  
Respiratory Rate ◽  
Half Life ◽  
Life Time ◽  
Pharmacokinetic Parameters ◽  
Time Profiles ◽  
Concentration Time

Abstract Propofol, 2,6-diisopropylphenol, seems to be a good candidate as a fish anaesthetic, however, no study regarding propofol influence on fish has yet been reported. The aim of this study was to examine propofol pharmacokinetics in rainbow trout (Oncorhynchus mykiss) following bath exposure. Fish (n = 100) were exposed to an aqueous propofol bath at 12°C and 17°C; propofol concentration in the bath was 10 mg L−1. Plasma concentration-time profiles were determined using LC-MS, and pharmacokinetic parameters were calculated. Propofol was absorbed quickly at both temperatures. Its concentration reached 13.8±2.7 μg mL−1 and 16.1±2.1 μg mL−1 at 12°C and 17°C, respectively, during the first minute of exposure. Blood plasma propofol decreased rapidly to 6.8±0.7 μgm L−1 and 6.3±2.2 μg mL−1 at 12°C and 17°C respectively, during the first 10 minutes of the recovery. The half-life time of propofol was 1.5 h and 1.1 h at 12°C and 17°C, respectively. We found propofol anaesthesia in trout effective and safe. However, it caused a gradual decrease of respiratory rate, and therefore a specific anaesthesia protocol should be developed.

Covalent Complexes Between Low Molecular Weight Heparin Fragments and Antithrombin III – Inhibition Kinetics and Turnover Parameters

1983 ◽  
Vol 49 (02) ◽  
pp. 109-115 ◽  
Author(s):  
M Hoylaerts ◽  
E Holmer ◽  
M de Mol ◽  
D Collen
Keyword(s):  
Molecular Weight ◽  
Half Life ◽  
Low Molecular Weight Heparin ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Life Time ◽  
Low Molecular Weight ◽  
High Affinity ◽  
Plasma Half Life ◽  
Covalent Complex

SummaryTwo high affinity heparin fragments (A/r 4,300 and M, 3,200) were covalently coupled to antithrombin III (J. Biol. Chem. 1982; 257: 3401-3408) with an apparent 1:1 stoichiometry and a 30-35% yield.The purified covalent complexes inhibited factor Xa with second order rate constants very similar to those obtained for antithrombin III saturated with these heparin fragments and to that obtained for the covalent complex between antithrombin III and native high affinity heparin.The disappearance rates from plasma in rabbits of both low molecular weight heparin fragments and their complexes could adequately be represented by two-compartment mammillary models. The plasma half-life (t'/j) of both low Afr-heparin fragments was approximately 2.4 hr. Covalent coupling of the fragments to antithrombin III increased this half-life about 3.5 fold (t1/2 ≃ 7.7 hr), approaching that of free antithrombin III (t1/2 ≃ 11 ± 0.4 hr) and resulting in a 30fold longer life time of factor Xa inhibitory activity in plasma as compared to that of free intact heparin (t1/2 ≃ 0.25 ± 0.04 hr).

Simultaneous optimization of activity and stability of xylose reductase from D. nepalensis NCYC 3413 using statistical experimental design

2020 ◽  
Vol 27 ◽  
Author(s):  
Shwethashree Malla ◽  
Sathyanarayana N. Gummadi
Keyword(s):  
Half Life ◽  
Specific Activity ◽  
Enzyme Stability ◽  
Reductase Activity ◽  
Xylose Reductase ◽  
Life Time ◽  
Economic Feasibility ◽  
Simultaneous Optimization ◽  
Physical Parameters ◽  
Statistical Experimental Design

Background: Physical parameters like pH and temperature play a major role in the design of an industrial enzymatic process. Enzyme stability and activity are greatly influenced by these parameters; hence optimization and control of these parameters becomes a key point in determining the economic feasibility of the process. Objective: This study was taken up with the objective to optimize physical parameters for maximum stability and activity of xylose reductase from D. nepalensis NCYC 3413 through separate and simultaneous optimization studies and comparison thereof. Method: Effects of pH and temperature on the activity and stability of xylose reductase from Debaryomyces nepalensis NCYC 3413 were investigated by enzyme assays and independent variables were optimised using surface response methodology. Enzyme activity and stability were optimised separately and concurrently to decipher the appropriate conditions. Results: Optimized conditions of pH and temperature for xylose reductase activity were determined to be 7.1 and 27 ℃ respectively, with predicted responses of specific activity (72.3 U/mg) and half-life time (566 min). The experimental values (specific activity 50.2 U/mg, half-life time 818 min) were on par with predicted values indicating the significance of the model. Conclusion: Simultaneous optimization of xylose reductase activity and stability using statistical methods is effective as compared to optimisation of the parameters separately.

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