High Quality Control Research Articles

BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR THE DETERMINATION OF ASCIMINIB ANTICANCER DRUG IN BIOLOGICAL MATRICES BY LC–ESI-MS/MS

Objective: A unique liquid chromatography-mass spectrometry technique is essential for determining the concentration of asciminib in biological matrices, and its development is of the utmost importance. Methods: The samples that were processed were separated using a Reversed Phase-Phenomenex (100 mm x 4.6 mm, 5 µm) C18 analytical column. The column was equipped with an isocratic moveable phase that consisted of 0.1% (v/v) HCOOH and acetonitrile at a ratio of 18:82% (v/v). The flow rate of the phase was 0.70 ml/min. For asciminib, the multiple reaction monitoring mode was used at m/z 450.23/257.3, while for canagliflozin, it was used at m/z 445.13/267.31. Results: With a correlation coefficient of 0.9998, the method was linear for asciminib throughout the concentration range of 1.0-2100.00 ng/ml. Each day's accuracy percentage relative standard deviation was within 5.74%. For analytes at the low-quality control level, the mean matrix factors ranged from 96.34 to 104.85% with a % Coefficient of Variance (CV) of 4.21; at the high-quality control level, the range was from 94.62 to 103.88% with a %CV of 3.67. Conclusion: The method that has been developed has the potential to be used to examine the pharmacokinetics and toxicokinetics of asciminib in various biological samples for both forensic and clinical purposes.

Saliva-based point-of-care assay to measure the concentration of pyrazinamide using a mobile UV spectrophotometer.

Pyrazinamide, one of the first-line antituberculosis drugs, displays variability in drug exposure that is associated with treatment response. A simple, low-cost assay may be helpful to optimize treatment. This study aimed to develop and validate a point-of-care assay to quantify the concentration of pyrazinamide in saliva. All measurements were conducted using the nano-volume drop function on the mobile ultraviolet (UV) spectrophotometer (NP80, Implen, Germany). Assay development involved applying second derivative spectroscopy in combination with the Savitzky-Golay filter between wavelengths of 200-300 nm to increase spectral resolution. Assay validation included assessing selectivity, linearity, accuracy, precision, carry-over and matrix effects. Specificity was also analysed by evaluating the impact of co-administered medications on pyrazinamide results. Sample stability was measured at various temperatures up to 40°C. The calibration curve (7.5-200 mg/L) was linear (R2 = 0.9991). The overall accuracy (bias%) and precision (CV%) ranged from -0.66% to 5.15%, and 0.56% to 4.95%, respectively. Carry-over and matrix effects were both acceptable with a bias% of <±4% and CV% of <7.5%. Commonly co-administered medications displayed negligible interferences. Levofloxacin displayed analytical interference (bias% = -10.21%) at pyrazinamide concentrations < 25 mg/L, but this will have little clinical implications. Pyrazinamide was considered stable in saliva after 7 days in all storage conditions with a CV% of <6.5% and bias% of <±10.5% for both low- and high-quality control concentrations. A saliva-based assay for pyrazinamide has been successfully developed and validated using the mobile UV spectrophotometer.

Bioanalytical method development and validation of docetaxel and carvacrol in mice plasma using LC-QqQ-MS/MS.

Present work describes the development of a liquid chromatography tandem mass spectrometry-based bioanalytical method for the reliable simultaneous quantification of docetaxel (DXL) and carvacrol (CVL) in the mice plasma. A rapid and sensitive bioanalytical method was developed and optimized in mice plasma using Paclitaxel as an internal standard. Validation of the bioanalytical method was performed according to the ICH M10 guideline covering the range of 9.62-1923.08 ng/mL in the mice plasma milleu at the low, mid, and high-quality control concentrations of 28.86 ng/mL, 961.54 ng/mL, and 1346.15 ng/mL, respectively for both the analytes. Validation parameters such as accuracy, precision, carryover-test, matrix effect, and reinjection reproducibility were carried out and were found in limits. Stability studies (Benchtop, autosampler, freeze-thaw, and long-term) were performed and found to be within limits. The developed bioanalytical method was found to be suitable for the simultaneous quantification of DXL and CVL in the mice plasma.

Insulin in aluminum phosphide poisoning: A systematic review of the current literature.

Aluminum phosphide (AlP) is a commonly used fumigant in agriculture and grain preservation because of its high potency and low cost. Due to the absence of a specific antidote and promising treatment modality, poisoning with this substance is deadly. Amid multiple studies in different parts of the world, each exploring options like lavage, inotropes, antioxidants, etc, we conducted a systematic review to find the possible role of exogenous insulin in treating symptomatic cases of AlP poisoning. Experimental studies released before February 15, 2024, that reported the use of exogenous insulin were systematically reviewed following the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. The search was done on PubMed Central, Cochrane Library, and Google Scholar. After applying the inclusion and exclusion criteria, we finalized a few scientific papers for the review. Studying data from 4 scientific papers (3 quasi-experimental studies and 1 randomized controlled trial), we could postulate the significant improvement in survivability after the inclusion of exogenous insulin in the treatment of poisoned cases of AlP. Studies showed divergent results for the blood pressure, blood gases, and need for mechanical ventilation. Hypoglycemia, hyperglycemia, and hypokalemia were the reported adverse effects of this therapy. Our review found that the use of exogenous insulin in AlP poisoning reduced mortality rates, which was consistent across all studies. With available knowledge, its inclusion as a part of therapy might be beneficial in AlP poisoning, but to put it forward confidently, we still need high-quality randomized control trials. It is indeed a subject of interest for future research.

A Liquid Chromatography‐Tandem Mass Spectrometry Bioanalytical Method Development and Validation for the Determination of Pacritinib in Plasma

ABSTRACTThe primary objective of the current work is to establish and verify an accurate and linear liquid chromatography‐electrospray ionization‐tandem mass spectrometry procedure for quantifying Pacritinib. An effective chromatographic resolution was obtained using the Hypersil Gold (50 × 4.6 mm, 2.1 µm) C18 column. The mobile phase is a mixture of methanol, 0.1% formic acid, and acetonitrile in the proportion of 20:15:65 (%v/v/v). The procedure involved closely monitoring executed ionic transitions of m/z 473.1/376.2 for Pacritinib and 584.26/101.1 for Brigatinib internal standard in multiple reaction monitoring mode. A strong correlation value (r2) of 0.9997 is associated with the linear plot regression line, which can be represented as y = 0.0001x − 0.0008. The relative standard deviation (RSD) results for the matrix effect were 3.63% and 3.57%, respectively, when the quality control (QC) level was low and high, respectively. Over the course of the study, the percentage average recoveries for Pacritinib were found to be 103.27% in high QC, 97.59% in medium QC, and 94.28% in low QC, respectively. The values that were obtained for the QC samples (0.378, 1.058, 7.56, and 11.34 µg/mL) varied from 2.00% to 4.03%. The developed method was useful for evaluating Pacritinib in biological samples for the purposes of QC, forensics, and bioavailability investigations for individuals.

B-297 Tacrolimus Concentrations in Envarsus vs Prograf Patients: An Evaluation of the Clinical Impact of LC-MS/MS and Immunoassay Methods on Tacrolimus measurement

Abstract Background Tacrolimus is a calcineurin inhibitor used as part of an immunosuppressive regimen in kidney and liver transplant patients to prevent graft-versus-host disease (GvHD) and requires therapeutic drug monitoring due to its narrow therapeutic index. Tacrolimus levels are commonly measured using two different methodologies - immunoassay and liquid chromatography tandem mass spectrometry (LC-MS/MS). A global proficiency study to assess and compare the measurement of trough levels by these two methodologies noted a positive bias with the ARCHITECT immunoassay which is likely due to the presence of tacrolimus metabolites. The aim of our study is to assess the impact of two different formulations of tacrolimus on the accuracy of its analytical measurement. While differences between immunoassay and LC-MS/MS results have been evaluated for immediate-release tacrolimus (Prograf), it has yet to be characterized for extended-release formulations such as Envarsus. The discrepancy between immunoassay and LC-MS/MS has clinical implications, as dosage modifications are based on measured concentrations, analytical variation may cause intervals of subtherapeutic or supratherapeutic exposure, increasing the risk of graft rejection or toxicity. Methods Development of an LC-MS/MS method for the simultaneous quantification of tacrolimus and its major metabolite, desmethyl tacrolimus, was performed in whole blood. Traceable calibrators and quality control material for tacrolimus and specimens supplemented with desmethyl tacrolimus were used to determine accuracy and precision. Tacrolimus concentrations were measured by LC-MS/MS and ARCHITECT immunoassay methods in excess whole blood specimens from patients treated with either Prograf or Envarsus. Measurement biases between LC-MS/MS and immunoassay methodologies were determined for both formulations of tacrolimus. Results External calibration curves for both tacrolimus and desmethyl tacrolimus were linear (R2&amp;gt;0.995), and the analytical measurement range (AMR) for tacrolimus spanned from 1.1 - 31.6 ng/ml. Calibrator and Quality control (QC) biases were within 15% of their target values throughout the AMR and within-run imprecision was less than 10% (n=25) for all calibrators and QCs. Between-run imprecision for Low, Mid, and High QC levels over a period of 2 weeks (n=5 days) was less than 10%. Comparative bias of tacrolimus concentrations between immunoassay and LC-MS/MS was significantly lower (P value=0.0074) for Envarsus (n=20 specimens) relative to Prograf (n=32 specimens). Conclusions The differential bias between immunoassay and LC-MS/MS in the measurement of tacrolimus in patients dosed with immediate-release versus extended-release formulations suggests that their distinct pharmacokinetic profile may impact the accuracy of the measurement. Therefore, applying observed measurement biases from different assays derived from Prograf patients to Envarsus patients and vice versa may result in erroneous estimation of tacrolimus concentrations.

Development of Community Economic Potential through Soybean Commodities in Sidorukun hamlet, West Stabat Lama Village, Langkat Regency

Most of the people in Sidorukun Hamlet depend on their livelihoods through the soybean commodity business which is then produced into tempeh, tofu, soy milk and tempeh crackers. This research aims to find soybean commodity products that have the most potential in developing the community's economy, as well as ways to increase the selling power and quality of soybean commodity products. This research is descriptive research using a qualitative approach. Data collection techniques in this research were carried out through observation and interviews. There were 6 informants in this study. The soybean commodity with the most potential is tempeh crackers, due to its longer shelf life and flexibility in distribution. To increase selling power, this can be done through e-commerce, diversifying products and brand image. In improving product quality, producers must have high quality human resources and routine quality control.

Investigating the contribution of image time series observations to cauliflower harvest-readiness prediction.

Cauliflower cultivation is subject to high-quality control criteria during sales, which underlines the importance of accurate harvest timing. Using time series data for plant phenotyping can provide insights into the dynamic development of cauliflower and allow more accurate predictions of when the crop is ready for harvest than single-time observations. However, data acquisition on a daily or weekly basis is resource-intensive, making selection of acquisition days highly important. We investigate which data acquisition days and development stages positively affect the model accuracy to get insights into prediction-relevant observation days and aid future data acquisition planning. We analyze harvest-readiness using the cauliflower image time series of the GrowliFlower dataset. We use an adjusted ResNet18 classification model, including positional encoding of the data acquisition dates to add implicit information about development. The explainable machine learning approach GroupSHAP analyzes time points' contributions. Time points with the lowest mean absolute contribution are excluded from the time series to determine their effect on model accuracy. Using image time series rather than single time points, we achieve an increase in accuracy of 4%. GroupSHAP allows the selection of time points that positively affect the model accuracy. By using seven selected time points instead of all 11 ones, the accuracy improves by an additional 4%, resulting in an overall accuracy of 89.3%. The selection of time points may therefore lead to a reduction in data collection in the future.

Variability in temperature control practices amongst the Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial

AimTemperature control is a complex bundled intervention; the synergistic impact of each individual component is ill defined and underreported. Resultantly, the influence of parameter optimization on temperature control’s overall neuroprotective effect remains poorly understood. To characterize variability in temperature control parameters and barriers to short pre-induction and induction times, we surveyed sites enrolling in an ongoing multicenter clinical trial. MethodsThis was a cross-sectional, survey study evaluating temperature control practices within the Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial (NCT04217551). A 23-question web-based survey (Qualtrics) was distributed to the site principal investigators by email. Respondents were asked about site practices pertaining to the use of temperature control, including the request to upload individual institutional protocols. Open-ended responses were analyzed qualitatively by categorizing responses into identified themes. To complement survey level data, records pertaining to the quality of temperature control were extracted from the ICECAP trial database. ResultsThe survey response rate was 75% (n = 51) including 23.5% (n = 12) survey respondents who uploaded institutional protocols. Most sites reported having institutional protocols for temperature control (n = 41; 80%), including 62.5% (n = 32) who had separate protocols for initiation of temperature control in the emergency department (ED). Fewer sites had protocols specific to sedation or neuromuscular blockade (NMB) management (n = 35, 68.6%). Use of NMB during temperature control induction was variable; 61.7% (n = 29) of sites induced paralysis less than 20% of the time. While most institutional protocols (n = 11, 83.3%) commented on the importance of early initiation of temperature control, this was incongruent with the largest reported barrier, which was clinical nihilism regarding the importance of early temperature control initiation (n = 30, 62.5%). Within the ICECAP trial database, 1 in 2 patients were treated with NMB however, use of NMB and time to initiation of temperature control device varied widely between sites. ConclusionAmongst ICECAP trial sites, there was significant variability in resources, methods, and barriers for early temperature control initiation. Defining and standardizing high-quality temperature control must be prioritized, as it may impact the interpretation of past and current clinical trial findings.

Development of a UPLC-MS/MS Method to Simultaneously Measure 13 Antiepileptic Drugs with Deuterated Internal Standards.

The goal of this study was to develop and validate a UPLC-MS/MS method for simultaneous mea-surement of 13 AEDs, including carbamazepine, oxcarbazepine, lamotrigine, levetiracetam, topiramate, primidone, zonisamide, gabapentin, lacosamide, perampanel, pregabalin, rufinamide, and vigabatrin, in whole blood samples. A UPLC-MS/MS method for simultaneous determination of 13 AEDs in whole blood was developed, and validation was conducted for accuracy, precision, limit of quantification (LOQ), matrix effect, and stability. Our method was compared to two different hospitals using UPLC-MS/MS. All AEDs exhibited linearity across the AMR (analytical measurement range), with R2 values ranging from 0.994 to 1.000. The imprecision and inaccuracy for low and high quality control (QC) levels were within an acceptable range, with the coefficient of variation (CV) < 15%. The LOQ was 0.62 µg/mL for carbamazepine, 1.61 µg/mL for oxcarbazepine, 1.30 µg/mL for lamotrigine, 13.20 µg/mL for levetiracetam, 1.26 µg/mL for topira-mate, 1.01 µg/mL for primidone, 1.59 µg/mL for zonisamide, 1.09 µg/mL for lacosamide, 1.61 µg/mL for gabapentin, 0.50 µg/mL for pregabalin, 0.07 ng/mL for perampanel, 3.00 µg/mL for rufinamide, and 2.06 µg/mL for vigabatrin. All AEDs demonstrated acceptable assay parameters for carryover, stability, and matrix effects. Moreover, the assay showed satisfactory results compared to two different hospitals with a bias of less than 15%. We successfully developed and validated a fast and robust UPLC-MS/MS method for routine therapeutic drug monitoring of thirteen antiepileptic drugs simultaneously.

ПЕРЕТВОРЮВАЧ АСИНХРОННОГО ЕЛЕКТРОПРИВОДА ТА ЕЛЕКТРОПРИВОДА ПОСТІЙНОГО СТРУМУ

A converter is considered that canprovide control of both anasynchronous electric drive and a DC electric drive. In an asynchronous electric drive control of a three-phase frequency converter by reactive power; in a DC electric drive the armature voltage is formed by PWM modulation of two arms of the frequency converter, and the voltage of the field winding is PWM modulated by the third arm of the converter. Ensures high-quality control of electric drives. Ref. 10, fig. 3.

Potential use of Six Sigma metrics in the quality control review of hospital glucose meters

Background and aimThis study applied Six Sigma metrics to facilitate the quality control (QC) review for hospital glucose meters. Materials and methodsQC data from a period of six months on all hospital glucose meters were extracted from the data management system. Sigma values for each meter at two QC levels were calculated and evaluated each month by combining the imprecision, the absolute bias between the meter mean and all-meter mean, and the standards from ISO 15179:2013. The effectiveness of using Sigma values in identifying meters with possible quality problems for further Levey-Jennings QC chart review was assessed. ResultsMore than 80 % of the meter's Sigma values within the six months were greater than 4 at either QC level. At the high QC level, twice as many Sigma values were below 4 than the low QC level. Including Sigma values 4, 3.5 or 3 in the criteria for the QC review reduced the number of chart review to 32.8 %, 11.2 % or 3.5 %, respectively. ConclusionsThe majority of the glucose meters examined in this study demonstrated optimal Sigma values. The Sigma metrics-based approach could be a valuable tool to guide an effective QC review of glucose meters for quality improvement.

Expert consensus on the key technologies for a multi-point trigger intelligent surveillance and early warning system for infectious diseases

An effective infectious disease surveillance and early warning system is a crucial component of public health safety and is essential for preventing and controlling outbreaks of infectious diseases. Enhancing surveillance and early warning capabilities is an urgent priority for advancing high-quality disease prevention and control efforts. Combining the research findings and practical experiences of experts in epidemiology, clinical medicine, disease prevention and control, data science, and computer science, and following multiple rounds of expert discussions, we have developed a consensus on the key technologies for a multi-point trigger intelligent surveillance and early warning system for infectious diseases. This consensus primarily covers the related concepts and definitions of the multi-point trigger intelligent surveillance and early warning system for infectious diseases, the key technical framework, sources, acquisition, and governance of multi-channel warning data, classification of early warning methods, multi-point trigger intelligent surveillance and early warning paths, multi-point trigger warning and comprehensive assessment, response to warning signals, and evaluation of early warning effectiveness. It aims to provide technical references for the construction and application of a multi-point trigger intelligent surveillance and early warning system for infectious diseases.

Intravenous ferric carboxymaltose versus oral ferrous sulphate for the treatment of moderate to severe postpartum anaemia in Nigerian women (IVON-PP): protocol for an open-label randomised controlled type 1 hybrid effectiveness-implementation trial

IntroductionPostpartum anaemia is often caused by iron deficiency with onset during the antepartum period and can be exacerbated by excessive blood loss at birth. Its prevalence is estimated as 50–80%...

The impact of digitalization on operational risk: An organizational information processing perspective

Digitalization has emerged as a mitigation tool for business risks. However, digitalization has not been effectively utilized because the mechanism of digitalization mitigating risks is still in the dark box. Drawing upon organizational information processing theory, we propose that digitalization reduces operational risk through internal control systems and supply chain networks (SCN). Based on the data of Chinese public firms from 2010 to 2019, we confirm that both improving internal control system quality and reducing SCN centrality are effective vehicles to help digitalization combat operational risk. Specifically, a high degree of digitalization leads to high-quality internal control systems, which, in turn, leads to low operational risk. Inversely, digitalization increases SCN centrality, which, in turn, leads to high operational risk. Furthermore, the positive mediation effect of SCN centrality is significantly more substantial than the negative mediation effect of internal control system quality. Subsequent moderating effect analysis shows that diversification does not impact the mediation effect of internal control system quality but strengthens the mediation effect of SCN centrality. This study deepens the understanding of the risk mitigation effect of digitalization and offers meaningful metrics for managers to prevent firms from suffering unexpected risks.

High Throughput Quality Control Tools for Carbon-Related Materials: A Raman Approach

Carbon-based materials play a pivotal role in battery technology, serving as negative electrode materials, conductive additives, and coating layers for both positive and negative electrode materials. Traditional characterization methods, such as transmission electron microscopy (TEM) and X-ray diffraction (XRD), fall short in providing comprehensive quality control, especially when distinguishing the structure of amorphous carbon materials. Raman spectroscopy as a convenient, simple tool is widely used to study the structure of carbon materials. It provides insights into the degree of crystallization, doping degree, and subtle structural differences arising from various preparation processes. By quantifying Raman spectrum testing results through statistical methods and providing relevant statistical outcomes, we demonstrate the potential of Raman spectroscopy as a quality control method for carbon material characterization. With extensive sample testing and automation, along with standardized spectral data processing and analysis software, we propose Raman spectroscopy as a suitable tool for high-throughput quality control in industrial production.

Migration agenda of the Kaliningrad region in the context of socio-economic development of Russia

Relevance. The socio-economic context of the importance of migration policy is represented by a wide range of areas. First of all, the intensity of migration processes significantly correlates with the state of the labor market, influencing the balance of supply and demand. The relevance of the research topic is due to the importance of migration policy, both for the socio-economic development of the state and for ensuring national security in the strategic management horizon. The importance of building an effective migration policy has a significant level of importance for modern Russia. Taking into account the author’s position, the geopolitical situation and the retrospective history of international communications make Russia the center of gravity of migration flows, which requires the establishment of high-quality control not only over their intensity, but also over their structural content.The purpose is to determine the most effective tools for improving migration policy, taking into account territorial specifics.Objectives: to clarify the theoretical and methodological aspects of the implementation of state migration policy in Russia; reveal the features, analytical indicators and organizational mechanisms for implementing migration policy in Russia, taking into account the territorial specifics of the Kaliningrad region.Methodology. The methodological “portfolio” of the study is built on the basis of the provisions of socioeconomic theories of migration process management using quantitative methods of data collection and analysis.Results. A targeted analysis was carried out, as a result of which effective tools were identified for improving migration policy in the Kaliningrad region based on the adaptation of the universal migration project in the Kaliningrad city management system, creating the prerequisites for increasing its effectiveness and achieving target indicators.Conclusion. Improving migration policy is an objective necessity in order to solve a number of socio-economic problems and minimize risks to national security.

Three years' registry on myocardial perfusion imaging patients in Ain shams university nuclear cardiology unit

Abstract Background The development in nuclear myocardial perfusion imaging (MPI) has provided diagnostic and prognostic implications in CAD patients, leading to an explosive increase in the performanceofthesestudies. Thisexpansionofimagingspectrumisassociatedwithwidespread concern regarding imaging utilization and increased healthcare costs. There is no comparative data that guide the use of these modalities with respect to appropriateness and patients’ benefit. Targeted data collection, through registry studies, enable analysis of both quality and outcomes with big advantages of reflecting real world daily practice and identifying the gaps in care which may not otherwise be feasible in high-quality randomized control trials. Objective To explore the extent to which stress myocardial perfusion imaging (MPI) studies met published appropriate use criteria (AUC), and the real world practice in the nuclear cardiology unit of Ain shams University. Patients and Methods It was a retrospective cohort study that included 2598 patients who underwent myocardial perfusion imaging in Ain Shams university nuclear cardiology unit throughout the period from January 2017 to December2019. All patients were subjected to thorough demographic data, history of cardiovascular risk factors (arterial hypertension, diabetes mellitus, smoking, family history of premature cardiovascular diseases), indication of the test, preprocedural ECG, ejection fraction by echocardiography, previous coronary angiography and PCI or CABG, calculation of pretest probability and Framingham risk score, determination of appropriateness use criteria and stress-rest Tc 99m imaging to detect the presence of ischemia and one day Tc 99m imaging to detect viability. Results The study included 2598 patients with mean age of 57.76 years, with male predominance (68.1%), 38.2% were diabetics and 53% had hypertension. The most common indications to undergo MPI was the exclusion of CAD as a cause of chest pain in 38.8% of patients followed by the evaluation of symptomatic post PCI patients in 21.9%. Moreover 63.8% of patients showed appropriate tests, while 18.6% of patients showed uncertain tests. Whereas 17.6% of patients had inappropriate studies. 81% of appropriate tests showed positive results of SPECT. Whereas in the inappropriate and the uncertain category, the negative test for ischemia predominated. Conclusion We have established that appropriateness criteria are effective in identifying appropriateness of SPECT in a university center located in Cairo. Also, we concluded that in our unit the appropriate tests were more prominent than inappropriate and unclassified tests. Most of the appropriate studies were positive for ischemia. While, most of the inappropriate and uncertain tests were normal and the commonest cause of referral for MPI was exclusion of CAD as a cause of chest pain.

A simple and sensitive LC-MS/MS method for the determination of loganic acid in rat plasma and its pharmacokinetic analysis.

Loganic acid is an iridoid compound extracted from Gentianaceae plant Gentiana macrophylla Pall. It can effectively inhibit inflammation and tumor migration and has antioxidant activity. In this paper, we establish a simple, fast, sensitive and validated LC-MS method with the purpose of quantification of loganic acid in rat plasma with gliclazide as an internal standard (IS). Methanol was used to precipitate the protein in the plasma sample, and a C18 column (2.1 × 50 mm, 1.7μm) was used for the separation of the target compound. Meanwhile, 0.1% formic acid water-methanol was employed as the mobile phase. Multiple reaction monitoring detection mode was adopted in detection with m/z 375.1 > 213.2 for loganic acid and m/z 322.1 > 169.9 for the IS, respectively, in negative ion scan mode. The linear range of calibration curve was 5.77-11,540.00 ng/ml, and the lower limit of detedtion was 2.89 ng/ml. The inter-day and intra-day precision and accuracy were <15% for lower limit of quantitation, low, middle and high quality control samples. This method was successfully used for the pharmacokinetic study of loganic acid in rat plasma at a dose range of 50-150 mg/kg for oral administration and 2mg/kg for intravenous administration. The pharmacokinetic results showed that the oral bioavailability of loganic acid was low (2.71-5.58%).

Credit default risk, internal control and stock returns

This paper selects the data of China's A-share listed companies from 2012 to 2022 as a research sample to explore the relationship between the credit default risk of listed companies and stock return. It is found that the credit default risk of listed companies hurts stock return; enterprises with high quality of internal control motivate enterprises to carry out effective risk management and reduce the impact of credit default risk on enterprise operation compared with state-owned enterprises, the negative effect of credit risk on stock return is more significant in non-state-owned enterprises.