Mean Recovery Research Articles

Evaluating Sperm Recovery Time and Efficacy of Monotherapy vs. Combination Therapies in Men with Congenital Hypogonadotropic Hypogonadism: A Systematic Review and Meta-Analysis.

There is a lack of pooled data exploring the time and rates for human chorionic gonadotropin (hCG) monotherapy vs. combination therapies (hCG+human menopausal gonadotropin or recombinant human follicle-stimulating hormone) to restore spermatogenesis in azoospermic men with congenital hypogonadotropic hypogonadism (CHH). We aimed to investigate the time and rates to recover spermatogenesis among azoospermic CHH men receiving monotherapy vs. combination therapy. We conducted a systematic review and meta-analysis following the PRISMA guidelines. The search was performed on PubMed, EMBASE, Web of Science, and Scopus databases up to November 2023. Forrest plots were generated to visually present the pooled effect sizes for time to recover spermatogenesis, specifically employing the standardized mean difference (SMD). Publication bias was assessed utilizing funnel plots. PROSPERO ID: CRD42023473615. The search identified 720 studies meeting inclusion criteria. Our meta-analysis of 1,240 men with CHH revealed significant differences in the time to recover spermatogenesis between combination therapies and monotherapy. The weighted mean recovery time was significantly shorter for combination therapies (10 months) compared to monotherapy (33 months). The SMD under the common effect model was 8.8 for combination therapies and 24.98 for monotherapy, indicating a more rapid recovery with combination therapies, p<0.01. The rates of sperm recovery were 66.76% for combination therapies and 51.9% for monotherapy, p=0.03. Significant heterogeneity was observed in both groups (I²=86% for combination therapies and I²=68% for monotherapy), suggesting considerable variation in individual responses. The present meta-analysis reveals that in men with CHH, combination therapies expedite spermatogenesis recovery more than monotherapy. Additionally, combination therapies yield a higher rate of sperm appearing in the ejaculate as compared to hCG monotherapy. The significant heterogeneity observed in both groups underscores the variability in individual responses, warranting further investigation and caution in interpreting these results.

Cyclodextrin-enhanced photo-induced fluorescence of tau-fluvalinate, molecular modelling of inclusion complexes and determination in natural waters.

The effect of adding organized supramolecular systems such as β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) on the photochemically-induced fluorescence (PIF) spectral properties of tau-fluvalinate (TFV) in aqueous solutions was examined. The influence of pH, UV irradiation time and photoproduct stability on the cyclodextrin-enhanced photochemically-induced fluorescence intensity was also investigated. The spectral changes associated with the inclusion process yielded values for the formation constants of TFV inclusion complexes between 450 and 640 M-1, which were calculated using the nonlinear iterative regression approach least squares. In addition, host-guest interaction was clearly determined by PIF enhancement and a 1 : 1 stoichiometry was found for the β-CD and HP-β-CD complexes formed with TFV. The negative free energy (ΔG°) value indicated that the reaction of TFV with cyclodextrins was thermodynamically favorable. Furthermore, the structures of inclusion complexes of TFV with cyclodextrins were elucidated by 3-21G ab initio calculations. The limits of detection and quantification obtained ranged between 1.3 and 4.0 ng mL-1 and from 4.4 to 13.0 ng mL-1 in β-CD and HP-β-CD media, respectively. The analytical application in tap and river water samples yielded satisfactory mean recoveries ranging from 98.12 to 102.97%. Due to its sensitivity and ease of use, this method can be reliably applied to routine analysis.

Simultaneous Estimation of Curcumin and Gentamicin by UV-VIS Spectrometric Methods or Derivative Spectroscopic Techniques

A simultaneous study is very important analytical parameter which helps to assess compatibility of mixture of drugs. UV spectrophotometer is one of the simplest and efficient methods to assess simultaneous parameters. Due to its economical approach, we have used UV spectrophotometer. Curcumin and Gentamicin sulphate have zero crossing points of 420 nm and 244 nm, respectively, in first-order derivative spectroscopy. The solvent for the spectrophotometric process was 0.1 N NaOH. Curcumin and Gentamicin sulphate linearity was established over range of concentrations of 2–12 g/ml, with correlation coefficients of 0.995 and 0.993. The mean percent recoveries Curcumin and Gentamicin sulphate were found to be in the range of 98.88 percent and 98.54 percent, respectively. The approach has been found to be repeatable in both inter day and intraday testing. The approach was proven to be both precise and reliable. According to the recovery investigation, the approach was effectively applied to pharmaceutical formulation with no interference from excipients. The results of the analysis were statistically evaluated, as well as by recovery trials. The LOD and LOQ for Gentamicin sulphate in phosphate buffer were found to be 0.024µg/ml and 0.045µg/ml, respectively and values for Curcumin were 0.024µg/ml and 0.037 µg/ml, respectively which indicates adequate sensitivity of method

The influence of Q.Clear reconstruction on the contrast recovery coefficient and semi-quantitative parameters of NEMA phantom imaging

Background: The aim of the study is to optimise the value of B parameter (β), which is used in the Q.Clear reconstruction in the imaging of neuroendocrine tumours. The study is divided into two parts: analysis of phantom data aiming at selection of the appropriate β for small changes, and then assessment of its impact on the quality of patients' images. The literature data on the optimal β value are inconclusive. Furthermore, the suggested values are not the result of the semi-quantitative assessment of Standard Uptake Volume (SUV) or the proper verification based on, for example, phantom studies using the known activity. Results: The obtained results show that β increase raises the image uniformity in the Q.Clear reconstruction algorithm. Also, referring to the scientific reports, one can see that the signal to noise ratio in the image increases. The effect of the β change on the SUV mean and Contrast Recovery Coefficient (CRC) value is greatest for the smallest objects. The decrease of this parameter is also much higher with lower values of activity (a lower counts statistic in the PET system). Conclusions: An increase of β has an adverse effect on the quality of a semi-quantitative assessment of SUV – as the parameter increases, the SUV and CRC values decrease. In the visual assessment, a satisfactory image quality is present with β = 450. Based on the analysis of SUV and CRC, an appropriate range of β values was selected as 350–450. At the selected range, a retrospective analysis of the clinical images of neuroendocrine tumours will be performed in the future and the impact of the change on the semi- -quantitative analysis of pathological changes will be verified.

The Effects of Early Mobilization on Pain and Quality of Recovery in Patients Undergoing Laparoscopic Cholecystectomy Surgery:

Objective: This study was conducted to determine the effects of early mobilization on pain and quality of recovery in patients undergoing laparoscopic cholecystectomy.&#x0D; Materials and methods: Pretest-posttest experimental design with control group. This study was carried out at the General Surgery Inpatient Clinic of a state hospital between April 2021 and January 2022. A total of 90 patients were included in the study. Starting with two hours after surgery, the patients in the experimental group were mobilized at least 6 times in 24 hours. A “Patient Description Form”, the “Visual Analog Scale for Pain”, and the “Quality of Recovery-40 Questionnaire” were used to collect data. &#x0D; Results: The introductory and medical characteristics of the patients in the intervention and control groups were similar. There was no significant difference between the pain and recovery quality mean scores of the patients in the two groups at the 2nd postoperative hour. The mean pain scores of the patients in the intervention group at the 24th hour and on the 15th day after surgery were found to be significantly lower than the scores of those in the control group. It was found that the mean recovery quality scores of the patients in the intervention group at the 24th hour and on the 15th day after surgery were also higher than those of the patients in the control group.&#x0D; Conclusions: It was determined that early mobilization reduced the level of pain and increased the quality of recovery in laparoscopic cholecystectomy patients.

Validation of a Targeted LC-MS/MS Method for Cereulide and Application in Food and Faeces.

Cereulide is an emetic toxin produced by some strains of Bacillus cereus. This bacterial toxin, a cyclic 1.2 kDa dodecadepsipeptide, is stable to heat and acids and causes nausea and vomiting when ingested via contaminated food. This work aimed to develop and validate a targeted analytical method applying liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify this toxin in food and human faeces. Samples were extracted with acetonitrile in the presence of 13C6-cereulide, a labelled internal standard, and purified by centrifugation and filtration. The limits of quantification were 0.5 and 0.3 µg kg-1 for food and faeces, respectively. The linearity of the method was very good, with calculated R2 values above 0.995. The mean recovery of the method was within the acceptable range of 70.0%-120.0%, the repeatability was not higher than 7.3%, and the highest intra-laboratory reproducibility was 8.9%. The estimated range for the expanded measurement uncertainty was between 5.1% and 18.0%. The LC-MS/MS method was used to analyse one food sample (rice) from a Belgian foodborne outbreak and five faecal samples from patients with clinical symptoms after consumption of the contaminated rice. The levels of cereulide were 12.22 µg g-1 for food and between 6.32 and 773.37 ng g-1 for faecal samples.

Safe Application of 75% Trifloxystrobin-Tebuconazole as Water-Dispersible Granules in Paddy Based on Residue and Dietary Risk Assessment.

The present study describes the development of a highly effective approach for determining the residue distribution and dissipation of trifloxystrobin and tebuconazole, and their risk assessment in brown rice, husk, straw, and grain using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The current study provides considerable novel information regarding the safe utilization of a mixture of trifloxystrobin and tebuconazole in paddy production. The samples demonstrated a range of mean recoveries between 72% and 86%, with a 1.1-9.2% relative standard deviation (RSD). The limits of quantification (LOQ) and half-lives (t1/2) for brown rice, husk, straw, and grain were, respectively, established to be 0.001-0.01 mg/kg and 4.1-7.7 days. The concentrations of terminal residues in the brown rice, husk, straw, and grain were, respectively, found to be 0.02-0.05, 0.03-0.11, 0.02-0.07, and 0.02-0.05 mg/kg after being treated twice at 168.75 g a.i./ha with 21 and 28 days of pre-harvest intervals (PHIs). Trifloxystrobin and tebuconazole presented a non-negligible chronic risk to human subjects, as evidenced by a risk quotient (RQ) value of less than 1.

Development of Stability Indicating Method for the Quantification of Futibatinib in K2EDTA Human Plasma by LC-MS/MS

sensitive, accurate, and linear LC-MS/MS method for the quantification of futibatinib in human plasma K2 ethylene diamine tetraacetic acid (EDTA) was developed. A Phenomenex C18, 150×4.60 mm, 2.1 μ column, 0.1% HCCOH, ACN and methyl alcohol (13/67/20, v/v/v) mobile solvent system at 0.8 mL/min was employed for the isolation of components.10 μL. of volumes were employed to isolate the peak responsess within 2.0 minutes at 40 ± 5ºC of oven temperature. Analyte retention was 1.261 minutes and ISTD of 1.292 minutes. Throughout the process of validation, each of the four calibration curves exhibited linear behavior for standards with concentrations ranging from 0.16 to 3250 ng/mL. Validation showed an r2 = 0.9997. At MQC, HQC, and LQC concentrations, futibatinib had 98.49, 99.35, and 98.47% mean recovery. Every QC level had a mean recovery of 90.51% and a %CV of 3.06. All of the control solutions had back-calculated concentration values that were accurate between 94.61 and 98.86% of the time. The range of %CV of back-calculated values for all quality control samples were in the range of 0.6 and 4.63, which is within the acceptable range of 15%. The developed method can be applied successfully for the quantification of the Futibatinib in biological matrices.

Ranolazine Quantification in Human Plasma: A QbD-Guided LC-MS Method Development and Validation

The present research outlines a comprehensive and systematic approach for the development and validation of a bioanalytical Liquid chromatography–mass spectrometry (LC-MS) method to quantify ranolazine in human plasma. The study employs principles of quality by design (QbD) to enhance method robustness, precision, and accuracy. The primary goals of this research were to create a reliable LC-MS method for the accurate quantification of ranolazine in human plasma and to validate this approach in accordance with established standards set by regulatory bodies. A secondary objective was to explore the application of QbD principles to optimize method performance. The study resulted in the successful development of an LC-MS method that exhibits exceptional specificity, sensitivity, accuracy, and precision in the quantification of ranolazine in human plasma. Specificity tests revealed no interference from endogenous plasma components. The method demonstrated good sensitivity with limit of quantitation (LoQ) of 5 ng/mL and limit of detection (LoD) of 2 ng/mL. Accuracy, as assessed through recovery studies, showed mean recoveries of 98, 99, and 101% for three different spiked concentrations. Precision, expressed as RSD, was below 5% for both intra-day and inter-day analyses. Linearity studies resulted in a calibration curve with an R² value of 0.9998. By employing QbD principles, the method demonstrated improved robustness, thus minimizing the impact of variability during sample analysis. Robustness experiments revealed minimal effects on precision and accuracy when varying critical parameters. This research not only presents a reliable LC-MS method for ranolazine quantification but also underscores the importance of incorporating QbD principles in bioanalytical method development. The validated method holds significant implications for clinical research, pharmacokinetic studies, and therapeutic drug monitoring. By enhancing the accuracy and robustness of ranolazine quantification, this method contributes to the advancement of pharmaceutical and clinical research, ultimately benefiting patient care and treatment outcomes.

Development of Novel RP-HPLC Method for Estimating Tepotinib in Bulk and Pharmaceutical Dosage Form

Objective: The study’s goal is to develop a highly appropriate, fast, precise, and validated reverse-phase high-performance liquid chromatography (RP-HPLC) approach that indicates stability for the estimation of tepotinib in pharmaceutical dosage form and bulk, in accordance with ICH recommendations. Method: The components were separated by chromatography using a Phenomenex Kinetex XB-C18 (150×4.6 mm, 5μ) column. The absorbance was measured at 272 nm, and the flow rate was 1.0 mL̸min. The International Council for Harmonisation (ICH) states that checks were made for linearity, precision, accuracy, system appropriateness, specificity, and protocol robustness. Results: Tepotinib was shown to have a retention period of 3.4 minutes. The results showed that the linearity ranged from 5 to 25 μg/mL (r2 = 0.9993), and the percentage mean recoveries for tepotinib’s accuracy and precision fell within the range of (%RSD˂ 2). It was discovered that the Limit of Detection (LoD), and Limit of Quantitation (LoQ) were, respectively, 0.429 and 1.3 μg/mL.

Antibacterial Effect of Basil (Ocimum basilicum) and Table Salt as Alternative Disinfectants against Staphylococcus aureus

This study was undertaken to evaluate the potency of basil (Ocimum basilicum) extract and table salt as alternative disinfectants based on their effect in inhibiting bacterial proliferation. A sample of bacteria (Staphylococcus aureus) with an initial mean density of 1.35 x 103 CFU/mL was used as the bacterial test culture. Treatments included basil extract (T1), table salt (T2), ethanol (T3, positive control) and distilled water (T4, negative control). The antibacterial effect of the treatments was evaluated in terms of the measurement of the zones of inhibition which was further validated by monitoring the mean recovery counts of bacteria post-application with the treatments given at different concentrations (100, 50, 25 and 10%). The results showed that the larger diameter of the zones of inhibition (with mean measurements that ranged from 17.65 to 20.98 mm) was related to the application of basil extract, table salt and ethanol applied at 100% concentration compared with the 50% (mean measurements ranged from 14.03 to 17.67 mm) underscoring the minimum inhibitory concentration of the candidate disinfectants at 50%. There was a comparable significant reduction of bacterial recovery counts associated with the application of basil extract and ethanol only at 3 h that were not sustained until 6 h. The results indicated that basil extract and table salt at the prescribed concentrations could be used and therefore recommended as disinfectants.

Unilateral transforaminal lumbar interbody fusion through a modified hemilateral spinous process-splitting approach.

To describe unilateral transforaminal lumbar interbody fusion (TLIF) via a modified hemilateral spinous process-splitting (MHSPS) approach and determine its effectiveness. Sixty-five consecutive patients with the lumbar degenerative disease who underwent MHSPS TLIF between August 2020 and July 2021 were retrospectively analyzed. Japanese Orthopedic Association (JOA) score and visual analog scale (VAS) scores for back and leg pain were evaluated before surgery and at the last follow-up. Postoperative paraspinal muscle atrophy was evaluated on axial T2-weighted magnetic resonance imaging. Mean JOA score increased from 13.6 ± 3.21 before surgery to 24.72 ± 3.34 at last follow-up (p < 0.001). The mean recovery rate was 68.2% ± 5.68%. Clinical outcome was excellent in 22, good in 35, and fair in 8 patients. The VAS score for low back pain was significantly lower at the last follow-up than before surgery (1.18 ± 0.99 vs. 3.09 ± 1.35; p < 0.001). The VAS score for leg pain was also significantly lower at the last follow-up than before surgery (1.13 ± 0.91 vs. 6.61 ± 1.23; p < 0.001). The mean paraspinal muscle atrophy rate did not significantly differ between the symptomatic side (6% ± 3.8%) and asymptomatic side (4.8% ± 3.3%) at last follow -up (p = 0.071). MHSPS TLIF is an effective minimally invasive surgical treatment for selected types of degenerative lumbar disease. This technique can achieve effective spinal decompression and interbody fusion. Its advantages include direct and adequate visualization, vast surgical working space, short operation time, and minimal muscle injury.

Absorption, Distribution, Metabolism, and Excretion of [14C]BS1801, a Selenium-Containing Drug Candidate, in Rats.

BS1801 is a selenium-containing drug candidate with potential for treating liver and lung fibrosis. To fully elucidate the biotransformation of BS1801 in animals and provide sufficient preclinical drug metabolism data for human mass balance study, the metabolism of BS1801 in rats was investigated. We used radiolabeling techniques to investigate the mass balance, tissue distribution, and metabolite identification of BS1801 in Sprague-Dawley/Long-Evans rats after a single oral dose of 100 mg/kg (100 μCi/kg) [14C]BS1801: 1. The mean recovery of radioactive substances in urine and feces was 93.39% within 168 h postdose, and feces were the main excretion route. 2. Additionally, less than 1.00% of the dose was recovered from either urine or bile. 3. BS1801-related components were widely distributed throughout the body. 4. Fifteen metabolites were identified in rat plasma, urine, feces, and bile, and BS1801 was detected only in feces. 5. BS1801-M484, the methylation product obtained via a N-Se bond reduction in BS1801, was the most abundant drug-related component in plasma. The main metabolic pathways of BS1801 were reduction, amide hydrolysis, oxidation, and methylation. Overall, BS1801 was distributed throughout the body, and excreted mainly as an intact BS1801 form through feces. No differences were observed between male and female rats in distribution, metabolism, and excretion of BS1801.

A SILAC-based accurate quantification of shrimp allergen tropomyosin in complex food matrices using UPLC-MS/MS

The carryover of trace allergens in complex food matrices poses challenges for detection techniques. Here, we demonstrate an accurate UPLC-MS/MS quantification assay for the shrimp allergen tropomyosin with a full-length isotope-labelled recombinant tropomyosin (TM-I) internal standard in complex food matrices. The TM-I, expressed based on the SILAC technique, exhibited a high isotope labelling ratio (>99%), purity, and alignment with the natural sequence. This method determined the tropomyosin ranging from 0.2 to 100 ng/mL. Mean recoveries ranged from 89 to 116%, with intra- and inter-day RSDs below 12%, for three signature peptides across three types of commercially processed food matrices. The limits of quantitation were 1 μg/g in pop food and sauce, and 10 μg/g in surimi product, respectively. This study supports the use of recombinant full-length isotope-labelled proteins rather than stable-isotope labelling peptides as internal standards to achieve more accurate quantitation of food allergens as the digestion error is corrected.

DETERMINATION OF TOXIC HEAVY METALS IN CHOLIC ACID USING QUADRUPOLE INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Objective: The information on the presence of toxic heavy metals in pharmaceutical starting materials and finished product is very crucial from the viewpoint of human life and its hazardous impact on the worldwide environment. The present work deals with the detailed quantification of the toxic heavy metals, namely, V, Co, Ni, Cd, Hg, Pb, and As, present in colic acid using quadrupole inductively coupled plasma mass spectrometry (Q-ICPMS) with prior microwave-assisted digestion. Moreover, the preliminary characterization of commercially available cholic acid by FT-IR, NMR (1H and 13C), SEM-EDAX has also been carried out. Methods: Cholic acid of synthesis grade, Nitric acid (65%) AR. grade, ethylene diamine tetra acetic acid sodium salt AR grade, and certified reference metal stock standard solutions (1000 mg/L) of multiple elements prepared in 2–3% HNO3 of analytical grade were purchased from Merck (Darmstadt, Germany). All the samples were treated with nitric acid and microwave-assisted digestion. For the accurate determination of the elemental amount, various digested solutions and post-digestion diluents were tested. The linearity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ) of the analytical technique were evaluated in accordance with the United States Pharmacopoeia 233 standard. Results and Discussion: The Q-ICPMS-based analytical method was validated for specificity, LOD, LOQ, linearity, accuracy, precision, and uncertainty. The estimated detection limits of the toxic heavy metals in cholic acid were in the range 2–180 μg/L. The quantification limits were in the range of 1.5–60 μg/L. Mean recoveries±standard deviations at different spiking levels were in the range 75.3±2.1–104.9±8.5%. The coefficients of variation were in the range of 0.5–8.1%. Conclusion: The precision of the analytical method, in terms of relative standard deviation, was below 1.95%. The uncertainty in the quantification of all the validated elements was found to be ≤1.70% for Sample 1.

DETERMINATION OF TOXIC HEAVY METALS IN CHOLIC ACID USING QUADRUPOLE INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Objective: The information on the presence of toxic heavy metals in pharmaceutical starting materials and finished product is very crucial from the viewpoint of human life and its hazardous impact on the worldwide environment. The present work deals with the detailed quantification of the toxic heavy metals, namely, V, Co, Ni, Cd, Hg, Pb, and As, present in colic acid using quadrupole inductively coupled plasma mass spectrometry (Q-ICPMS) with prior microwave-assisted digestion. Moreover, the preliminary characterization of commercially available cholic acid by FT-IR, NMR (1H and 13C), SEM-EDAX has also been carried out. Methods: Cholic acid of synthesis grade, Nitric acid (65%) AR. grade, ethylene diamine tetra acetic acid sodium salt AR grade, and certified reference metal stock standard solutions (1000 mg/L) of multiple elements prepared in 2–3% HNO3 of analytical grade were purchased from Merck (Darmstadt, Germany). All the samples were treated with nitric acid and microwave-assisted digestion. For the accurate determination of the elemental amount, various digested solutions and post-digestion diluents were tested. The linearity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ) of the analytical technique were evaluated in accordance with the United States Pharmacopoeia 233 standard. Results and Discussion: The Q-ICPMS-based analytical method was validated for specificity, LOD, LOQ, linearity, accuracy, precision, and uncertainty. The estimated detection limits of the toxic heavy metals in cholic acid were in the range 2–180 μg/L. The quantification limits were in the range of 1.5–60 μg/L. Mean recoveries±standard deviations at different spiking levels were in the range 75.3±2.1–104.9±8.5%. The coefficients of variation were in the range of 0.5–8.1%. Conclusion: The precision of the analytical method, in terms of relative standard deviation, was below 1.95%. The uncertainty in the quantification of all the validated elements was found to be ≤1.70% for Sample 1.

Residue analysis and dietary risk assessment of abamectin in fresh corn, bitter melon, and Fritillaria.

To clarify the residue behavior and possible dietary risk of abamectin in fresh corn, bitter melon, and Fritillaria, a method was developed for the simultaneous determination of abamectin residues in fresh corn, bitter melon, and Fritillaria by QuEChERS (quick, easy, cheap, effective, rugged, safe) ultra-performance liquid chromatography-tandem mass spectrometry. The mean recovery of abamectin in fresh corn, bitter melon, and Fritillaria was 86.48%-107.80%, and the relative standard deviation was 2.07%-10.12%. The detection rates of abamectin residues in fresh corn, bitter melon, and Fritillaria were 62.50%, 87.50%, and 80.00%, respectively. The residues of abamectin in fresh corn, bitter melon, and Fritillaria were not more than 0.020, 0.019, and 0.087 mg/kg, respectively. Based on these results, dietary risk assessment showed that the risk content of abamectin residues in long- and short-term dietary exposure for Chinese consumers was 61.57% and 0.41%-1.11%, respectively, indicating that abamectin in fresh corn, bitter melon, and Fritillaria in the market would not pose a significant risk to consumers.

Mass Balance and Metabolic Pathways of Eliapixant, a P2X3 Receptor Antagonist, in Healthy Male Volunteers.

Overactive adenosine triphosphate signaling via P2X3 homotrimeric receptors is implicated in multiple conditions. To fully understand the metabolism and elimination pathways of eliapixant, a study was conducted to assess the pharmacokinetics, mass balance, and routes of excretion of a single oral dose of the selective P2X3 receptor antagonist eliapixant, in addition to an invitro characterization. In this single-center open-label non-randomized non-placebo-controlled phase I study, healthy male subjects (n=6) received a single dose of 50mg eliapixant blended with 3.7MBq [14C]eliapixant as a PEG 400-based oral solution. Total radioactivity and metabolites excreted in urine and feces, and pharmacokinetics of total radioactivity, eliapixant, and metabolites in plasma were assessed via liquid scintillation counting and high-performance liquid chromatography-based methods coupled to radiometric and mass spectrometric detection. Metabolite profiles of eliapixant in human invitro systems and metabolizing enzymes were also investigated. After administration as an oral solution, eliapixant was rapidly absorbed, reaching maximum plasma concentrations within 2h. Eliapixant was eliminated from plasma with a mean terminal half-life of 48.3h. Unchanged eliapixant was the predominant component in plasma (72.6% of total radioactivity area under the curve). The remaining percentage of drug-related components in plasma probably represented the sum of many metabolites, detected in trace amounts. Mean recovery of total radioactivity was 97.9% of the administered dose (94.3-99.4%) within 14 days, with 86.3% (84.8-88.1%) excreted via feces and 11.6% (9.5-13.1%) via urine. Excretion of parent drug was minimal in feces (0.7% of dose) and urine (≈0.5%). In feces, metabolites formed by oxidation represented > 90% of excreted total radioactivity. The metabolites detected in the invitro experiments were similar to those identified invivo. Complete recovery of administered eliapixant-related radioactivity was observed in healthy male subjects with predominant excretion via feces. Eliapixant was almost exclusively cleared by oxidative biotransformation (>90% of dose), with major involvement of cytochrome P450 3A4. Excretion of parent drug was of minor importance (~1% of dose). ClinicalTrials.gov: NCT04487431 (registered 27 July 2020)/EudraCT number: 2020-000519-54 (registered 3 February 2020), NCT02817100 (registered 26 June 2016), NCT03310645 (registered 16 October 2017).

Meropenem extraction by ex vivo extracorporeal life support circuits.

Meropenem is a broad-spectrum carbapenem-type antibiotic commonly used to treat critically ill patients infected with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. As many of these patients require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), it is important to understand how these extracorporeal life support circuits impact meropenem pharmacokinetics. Based on the physicochemical properties of meropenem, it is expected that ECMO circuits will minimally extract meropenem, while CRRT circuits will rapidly clear meropenem. The present study seeks to determine the extraction of meropenem from ex vivo ECMO and CRRT circuits and elucidate the contribution of different ECMO circuit components to extraction. Standard doses of meropenem were administered to three different configurations (n=3 per configuration) of blood-primed ex vivo ECMO circuits and serial sampling was conducted over 24h. Similarly, standard doses of meropenem were administered to CRRT circuits (n=4) and serial sampling was conducted over 4h. Meropenem was administered to separate tubes primed with circuit blood to serve as controls to account for drug degradation. Meropenem concentrations were quantified, and percent recovery was calculated for each sample. Meropenem was cleared at a similar rate in ECMO circuits of different configurations (n=3) and controls (n=6), with mean (standard deviation) recovery at 24h of 15.6% (12.9) in Complete circuits, 37.9% (8.3) in Oxygenator circuits, 47.1% (8.2) in Pump circuits, and 20.6% (20.6) in controls. In CRRT circuits (n=4) meropenem was cleared rapidly compared with controls (n=6) with a mean recovery at 2h of 2.36% (1.44) in circuits and 93.0% (7.1) in controls. Meropenem is rapidly cleared by hemodiafiltration during CRRT. There is minimal adsorption of meropenem to ECMO circuit components; however, meropenem undergoes significant degradation and/or plasma metabolism at physiological conditions. These ex vivo findings will advise pharmacists and physicians on the appropriate dosing of meropenem.

Green Alternatives in Pharmaceutical and Bioanalytical Analysis of TDM Required Drugs: Procainamide.

In drug analysis, using non-hazardous solvents instead of the ones harmful to humans and the environment is a green strategy to protect analysts and environmental health. Procainamide (PCA) is an antiarrhythmic drug requiring therapeutic drug monitoring (TDM) because of its narrow therapeutic window and serious side effects. The aim of this study is to develop validated green HPLC methods to be used in drug quality control and TDM analysis for PCA, thus indicating the further applicability in the analysis of TDM-required drugs, such as immunosuppressants, anti-cancer drugs, and psychiatric drugs. Human-friendly ethanol was selected as an organic solvent in the mobile phase. PCA was eluted from NUCLEODUR 100-5 C8 ec (5 μm, 150 x 4.6 mm) column by a mobile phase containing ethanol and 50 mM NaH2PO4 buffer (5:95, v/v). The mobile phase flow rate was 1.0 ml min-1, the column temperature was 35 °C, and the wavelength at the PDA detector was 278 nm. Retention time for PCA was 5.0 min and 7.7 min for paracetamol as an internal standard (IS). In the green HPLC method for pharmaceutical analysis, the highest relative standard deviation (RSD) and mean recovery values were 1.32% and 98.89%, respectively. In the analysis of plasma, the sample preparation step was only smooth protein precipitation by ethanol. Thus, the bioanalytical method was fully green having a limit of detection (LOD) of 0.3 μg ml-1 and a limit of quantification (LOQ) of 0.8 μg ml-1. The therapeutic plasma concentration for PCA was reported in the range of 4-12 μg ml-1. As a result, the green HPLC methods developed and validated in this study were selective, accurate, precise, reproducible, and trustable and have the quality for the application in pharmaceutical and TDM analysis of PCA, thus encouraging green HPLC analysis of other TDM required drugs.