Investigation of a DNA Profiling Method Using Only Cementum More Than 70 Years After Death.

Short tandem repeat (STR) typing is widely used not only for blood relationship identification but also for the personal identification of unidentified bodies. However, DNA is susceptible to the effects of environmental factors, consequently leading to reduced DNA yields. Therefore, to maximize the DNA yield required for identification, teeth are generally completely pulverized during DNA extraction. However, this renders subsequent testing after DNA profiling impossible. In this study, we investigated the utility of DNA profiling using only the cementum from teeth that had been left outdoors for long postmortem intervals. We analyzed 90 molars (fresh teeth) that were extracted within six months at a dental clinic and 90 molars (stale teeth) exposed outdoors for over 70 years, and following cementum extraction, the accuracy of STR profiling, optimal site for cementum collection, and minimum amount of cementum required for STR profiling were determined. The results demonstrated that the profiling accuracy of DNA extracted from cementum was comparable to that of DNA from dental pulp and dentin. Furthermore, the collection of cementum from either near the cervical line or from the root apex areas did not show significant differences in DNA profiling accuracy, indicating that securing at least 5 mg of cementum was sufficient to ensure precise DNA profiling. These findings suggest that DNA profiling using only cementum is viable even in teeth that have been subjected to a long postmortem interval.

A case of Sjögren's syndrome in which diffuse cystic lung lesions led to an accurate diagnosis.

Key Clinical Message: Even in the absence of other symptoms or other pulmonary manifestations suggesting Sjögren's syndrome (SS), it is necessary to include SS in the differential diagnosis of diffuse cystic lung disease (CLD). Abstract: A case of SS that presented initially with diffuse CLD is reported. This case is considered rare because diffuse pulmonary cysts were observed in the early stage with few symptoms, only cysts were observed without other lung lesions on imaging, cyst formation was histologically considered to be alveolar loss, and airway lesions not observed on imaging were suspected based on lung function testing. The details of this case provide extremely important information to consider for the diagnosis and management of CLD and SS.

Patients with infusion-related reactions on fixed-dose rituximab treatment have higher body surface area than those without infusion-related reactions in adults with frequently relapsing minimal change nephrotic syndrome: a retrospective study.

BACKGROUND: Infusion-related reactions (IRRs) are major side effects of rituximab administration. Male sex, high body weight, body surface area (BSA), and body mass index are predictive markers of rituximab-induced IRRs. However, as rituximab was not administered at a fixed dosage in a previous study, whether a higher dosage or factors associated with a larger physique are more strongly associated with rituximab-induced IRRs is unknown. MAIN BODY: Thirteen adults with frequently relapsing minimal change nephrotic syndrome (MCNS) who received an initial rituximab dose of 500 mg between September 2015 and November 2022 were retrospectively evaluated. Data on IRRs were collected from medical records. The incidence of rituximab-induced IRRs was 38.5% (5/13). The IRR group had a significantly higher BSA than the non-IRR group (median, 1.86 vs. 1.48 m2; p = 0.045). Additionally, rituximab dosage normalized by BSA in the IRR group was significantly lower than that in the non-IRR group (median, 268.8 vs. 337.9 mg/m2; p = 0.045). CONCLUSIONS: Our study revealed that adults with frequently relapsing MCNS who experienced IRRs tend to have a higher BSA, even with fixed-dose rituximab treatment. Therefore, when patients with higher BSA receive rituximab treatment, clinicians should be careful about monitoring patient condition whether the dosage is fixed or not.

Analysis of Risk Factors for Febrile Neutropenia in Patients with Small-Cell Lung Cancer Receiving Carboplatin Plus Etoposide Therapy.

INTRODUCTION: Febrile neutropenia (FN) is an oncologic emergency requiring immediate empiric antibiotic therapy. Although carboplatin plus etoposide combination chemotherapy is associated with a relatively high frequency of FN, the risk factors are unclear. Hence, this retrospective study aimed to identify predictive markers of carboplatin/etoposide-induced FN. METHODS: We conducted a retrospective cohort analysis of patients with previously untreated small-cell lung cancer (SCLC) who received combination chemotherapy with carboplatin (area under the concentration curve: 5 mg/mL·min, day 1) and etoposide (80 or 100 mg/m2, days 1-3) between July 2007 and June 2022. FN was assessed during the 21 days after initiation of carboplatin and etoposide therapy according to the Japanese Society of Medical Oncology's definition. Fisher's exact test for categorical variables and Mann-Whitney U test for continuous variables were used to compare the two groups. Statistical significance was set at p values <0.05. Explanatory variables with p values <0.05 in the univariate analysis were included in the multivariate logistic regression analysis. RESULTS: Among the 176 eligible patients, the incidence of FN during the first cycle of chemotherapy was 25.0% (44/176). Multivariate analysis revealed that co-administration of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (PCABs) and body mass index (BMI) were significantly associated with FN (p = 0.0035 and 0.0011, respectively). Patients with both co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 presented with significantly higher frequencies of FN compared with the other patients (13/24 [54.2%] vs. 31/152 [20.4%] patients; odds ratio: 4.56, 95% confidence interval: 1.70-12.48; p = 0.00147). CONCLUSION: Patients who received carboplatin plus etoposide for SCLC with co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 more frequently present with FN than those without the two factors.

Influence of the amount of saliva deposition and time elapsed after deposition on bite mark analysis.

Bite mark analysis is among the most interesting research fields in forensic odontology; however, it is limited by its dependence on the employed method as well as assessor subjectivity, particularly when using morphological analysis or DNA profiling. These limitations are due to differences in DNA collected from saliva adhering to a living or inanimate body, as well as differences in exocrine fluid secretion and deposition amount among individuals. This study aimed to analyze the effectiveness of DNA profiling when there are differences in the amount of saliva adhering to a living body and when time has elapsed since deposition. Most allele peaks could be identified in 1 µl of saliva, even 9 h after saliva deposition and examination. Consistent results were obtained following saliva deposition in an individual who had engaged in up to 9 h of free activity. The results of this study demonstrate the validity and reliability of DNA profiling for bite mark analysis and are extremely important as they can demonstrate the usefulness of the little information left by a suspect on a victim's body.

Analysis of Risk Factors for Infusion-Related Reactions Following Rituximab Administration in Patients with Desensitization before Renal Transplantation.

Infusion-related reactions (IRRs) are the major side effects of rituximab administration. Although several studies have reported predictive markers for IRRs in patients with malignancies, there are no such reports for patients without malignancies. Accordingly, we aimed to clarify the predictive markers for rituximab-induced IRRs in renal transplant recipients. This retrospective study included 116 inpatients aged ≥18 years who received an initial dose of 150 mg/m2 of rituximab for desensitization before renal transplantation with loxoprofen and diphenhydramine before rituximab infusion between June 2007 and February 2022. Overall, 45 patients were evaluated and 71 patients were excluded in this study. IRRs were observed in 12 (26.7%) patients. The proportion of men in the IRRs group was significantly higher than that in the non-IRRs group (p = 0.023). Additionally, body weight, body surface area (BSA), and body mass index (BMI) were significantly higher in the IRRs group than in the non-IRRs group (body weight, p = 0.0058; BSA, p = 0.0051; BMI, p = 0.017). Their cutoff values for predicting rituximab-induced IRRs, based on the receiver-operating characteristic curve, were 74.850 kg, 1.910 m2 and 24.164 kg/m2, respectively. In conclusion, the male sex, high actual body weight, BSA, and BMI may be new predictive markers for rituximab-induced IRRs in renal transplant recipients. Therefore, clinicians should carefully monitor patients who receive rituximab before renal transplantation and present with the predictive markers.

Reliability and Validity of the Japanese Version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale in Kidney Transplant Recipients.

A valid and reliable instrument that can measure adherence is needed to identify nonadherent patients and to improve adherence. However, there is no validated Japanese self-report instrument to evaluate adherence to immunosuppressive medications for transplant patients. The purpose of this study was to determine the reliability and validity of the Japanese version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS). Methods: We translated the BAASIS into Japanese and developed the Japanese version of the BAASIS (J-BAASIS) according to the International Society of Pharmacoeconomics and Outcomes Research task force guidelines. We analyzed the reliability (test-retest reliability and measurement error) and validity of the J-BAASIS (concurrent validity with the medication event monitoring system and the 12-item Medication Adherence Scale) referring to the COSMIN Risk of Bias checklist. Results: A total of 106 kidney transplant recipients were included in this study. In the analysis of test-retest reliability, Cohen's kappa coefficient was found to be 0.62. In the analysis of measurement error, the positive and negative agreement were 0.78 and 0.84, respectively. In the analysis of concurrent validity with the medication event monitoring system, sensitivity and specificity were 0.84 and 0.90, respectively. In the analysis of concurrent validity with the 12-item Medication Adherence Scale, the point-biserial correlation coefficient for the "medication compliance" subscale was 0.38 (P < 0.001). Conclusions: The J-BAASIS was determined to have good reliability and validity. Using the J-BAASIS to evaluate adherence can help clinicians to identify medication nonadherence and institute appropriate corrective measures to improve transplant outcomes.

Prognostic Nutrition Index as an Indicator of Therapeutic Response to Lenvatinib Therapy in Hepatocellular Carcinoma.

BACKGROUND/AIM: Lenvatinib (LEN) has been approved as an oral tyrosine kinase inhibitor for advanced hepatocellular carcinoma (HCC). However, in some patients, LEN does not provide adequate therapeutic benefits. In this study, we examined the factors that affect the therapeutic response to LEN. PATIENTS AND METHODS: This retrospective cohort study involved patients with HCC who received LEN therapy at Osaka Metropolitan University Hospital. We used the delivered dose intensity to body surface area ratio for 60 days (2M-DBR) as an index of the therapeutic response. RESULTS: This study included 83 patients divided into two groups, the high 2M-DBR group (47 patients, 56.7%) and low 2M-DBR group (36 patients, 43.4%). Univariate analysis showed that Child-Pugh class, C-reactive protein, and prognostic nutrition index (PNI) were significant factors for high 2M-DBR. Furthermore, multivariate logistic regression analysis revealed that a PNI>39.15 was significantly associated with high 2M-DBR. CONCLUSION: A PNI cut-off value of less than 39.15 may indicate a poor response to LEN therapy. PNI, an easy, simple, and inexpensive tool, may be useful in identifying patients in need of early intervention.

A method for estimating time since death through analysis of substances deposited on the surface of dental enamel in a body immersed in freshwater.

Estimating the elapsed time after death of a corpse immersed in freshwater is often challenging owing to body temperature changes and the degree of postmortem lividity, and the tissues used for this assessment deteriorate drastically as the postmortem period progresses. In this study, assuming a corpse was immersed in freshwater, we analyzed changes in the amount of deposits on the enamel surface of teeth since the time of immersion using an electron probe microanalyzer. We calculated a regression equation for estimating the time of immersion in water (the time after death). We considered this approach would be useful to estimate the time after death even in rotting and skeletonized corpses from which only limited information could be obtained. This study was undertaken according to a previously reported method that used a regression equation for estimating the time after death of bodies found in a seawater area.

The Cyclin-Dependent Kinase 4/6 Inhibitor Abemaciclib Is Tolerated Better than Palbociclib by Advanced Breast Cancer Patients with High Serum Albumin Levels.

The cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib, have been approved in Japan. However, the selection criteria for these drugs have not been established. Hence, we aimed to identify the risk factors for CDK4/6 inhibitor-induced intolerable adverse events requiring dose reduction or therapy cessation and to establish useful markers for choosing the appropriate CDK4/6 inhibitor, based on the incidence of the intolerable adverse events. This retrospective cohort analysis included patients with advanced breast cancer who received 125 mg/d palbociclib or 300 mg/d abemaciclib. We defined significant adverse events (SAEs) as side effects requiring dose reduction or therapy cessation. Thirty-six percent of the patients who received palbociclib (9/25) and 27.3% of those who received abemaciclib (9/33) experienced SAEs. In palbociclib and abemaciclib groups, baseline white blood cell (WBC) counts and serum albumin (ALB) levels, respectively, were significantly lower in patients who experienced SAEs than in those who did not (palbociclib: p = 0.007; abemaciclib: p = 0.004). According to the receiver operating characteristic curve analysis, the optimal cutoff values for baseline WBC count and ALB level were 5700/µL and 4.0 g/dL, respectively. Among patients with ALB levels >4.0 g/dL, the incidence of abemaciclib-induced SAEs was significantly lower than that of the palbociclib-induced SAEs (1/17 (5.9%) vs. 6/14 (42.9%), odds ratio: 11.0, 95% confidence interval: 1.07-583, p = 0.0281). Thus, a baseline WBC count ≤5700/µL and ALB level ≤4.0 g/dL may be risk factors for palbociclib and abemaciclib-induced SAEs, respectively. Also, high ALB levels can serve as a useful marker for choosing abemaciclib.

Population pharmacokinetics of linezolid and its major metabolites PNU-142300 and PNU-142586 in adult patients.

INTRODUCTION: Only a few reports are available on the population pharmacokinetic (PK) analysis of linezolid and its main metabolites. Therefore, we investigated the population PK of linezolid and its metabolites in adult patients treated with intravenous linezolid to identify the causative factors affecting pharmacokinetics, and evaluated the relationship between the parent compound and major metabolites PNU-142300 and PNU-142586. METHODS: Population PK analysis was performed using medical data collected from patients who were treated with intravenous linezolid (600 mg twice daily). We examined the impact of covariate candidates such as demographic characteristics and laboratory parameters. Simulations using the final model were investigated and used to estimate the plasma concentrations, trough concentrations (Cmin ), and area under the curve (AUC) of linezolid and its metabolites, and the metabolite-to-parent ratios for Cmin and AUC were used to assess the accumulation of metabolites over linezolid. RESULTS: A total of 82 plasma concentrations from 23 patients were analyzed. The volume of distribution was estimated to be 47.1 L, assuming that linezolid and its metabolites were the same. The total clearance (CL) of linezolid, and CLs of PNU-142300 and PNU-142586 were influenced by creatinine clearance (CLcr), with population mean CLs of 3.86, 7.27, and 13.54 L/h, respectively. The Cmin and AUCs of linezolid and its metabolites and the ratios of metabolites per linezolid were predicted to increase exponentially with decreasing renal function. CONCLUSION: We developed the first population PK model in which CLcr was incorporated as a covariate in the CL of linezolid and its metabolites. Using the final model, it was possible to predict the plasma concentration, Cmin , and AUC appropriately. The model was found to be a potentially useful tool for future studies on optimal dosing and toxicity analysis.

New Method of Dental Personal Identification of Disaster Victims Using Oral Scanner.

Dentistry plays an important role in the identification of victims in large-scale disasters. The current poor status of and problems with victim identification work were highlighted in the aftermath of the Great East Japan Earthquake of March 11, 2011, in which some 10,000 people lost their lives. The techniques of dental identification therefore need to be improved if they are to cope with the problems associated with identification that will accompany the predicted Tokai earthquake and other unexpected large-scale disasters in the future. The purpose of this study was to determine the effectiveness of applying a digital impression-taking device employed in regular dental care to dental personal identification. The Trophy 3DI pro (Yoshida Dental) was applied to a total of 150 dental models. The diagnosis was accurate in 2,096 teeth from a sample of 2,100 comprising 1,240 non-treated teeth, 670 treated teeth, and 190 missing teeth, yielding a 99.8% level of statistical precision. These results suggest that the level of accuracy offered by this impression-taking device indicates that it would be a useful tool in establishing personal identification in disaster victims.

Body Mass Index of Elderly Patients with Normal Renal Function as a Determining Factor for Initial Vancomycin Regimen Designing.

INTRODUCTION: Currently, the use of actual body weight is recommended for dosing in vancomycin regimen designs, and it is important to perform therapeutic drug monitoring for efficacy and safety. However, the method to determine the appropriate vancomycin regimen for underweight or obese patients remains controversial. The aim of this study was to evaluate the impact of body mass index (BMI) on the relationship among vancomycin doses, trough concentration, and area under the curve (AUC). In addition, we identified the group of patients who were potentially more affected by BMI and evaluated the optimal dosing regimen to achieve the target AUC. METHODS: We retrospectively collected data from 462 patients who received vancomycin at the Osaka City University Hospital between January 2013 and September 2019. Patients were classified by their BMI group (underweight <18.5, normal weight 18.5-24.9, and obese ≥25.0 kg/m2). We assessed the association between vancomycin dose versus trough concentration or AUC as well as dose-adjusted trough concentration and AUC in each BMI subgroup to determine the doses for achieving the target AUC. RESULTS: The dose-adjusted trough concentration and AUC in elderly patients with normal renal function appeared to increase significantly with an increase in BMI (p < 0.05). Vancomycin doses that enabled the achievement of AUC400 in elderly patients with normal renal function decreased with increasing BMI: 17.7, 15.8, and 12.9 mg/kg per time in the underweight, normal weight, and obesity groups, respectively (p < 0.05). CONCLUSION: Elderly patients with normal renal function were the most affected by BMI on vancomycin trough concentration and AUC. The vancomycin regimen design in these patients should be adjusted carefully, not only based on the patient's renal function but also based on BMI.

Risk factors for acute kidney injury in vancomycin and piperacillin/tazobactam combination therapy: A retrospective study.

INTRODUCTION: Combined use of vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) has been reported to increase the incidence of acute kidney injury (AKI). However, the risk factors associated with AKI after VCM and PIPC/TAZ (VPT) administration have not yet been identified. Therefore, we retrospectively assessed patients treated with VPT to investigate the risk factors for AKI development. METHODS: The study involved patients who were treated with VPT from January 1, 2016 to March 31, 2020. The patients were divided into the AKI or non-AKI group. The clinical characteristics of patients and antimicrobial therapy were compared between the groups. Their association with AKI risk was evaluated using multivariate logistic regression analysis. RESULTS: In total, 182 patients were included, with 118 in the non-AKI group and 64 in the AKI group. Therefore, the incidence of AKI was 35.2 %. The initiation of VPT combination therapy on the same day and concomitant use of vasopressors were associated with an increased risk of AKI (odds ratio [OR] 2.55, 95 % confidential interval [CI] 1.20-5.44 and OR 3.22, 95 % CI 1.31-7.89, respectively). CONCLUSION: Our findings suggest that the concomitant use of vasopressors and initiating VPT combination therapy on the same day are likely risk factors for AKI development.

Personal Identification by Superimposition of Three-dimensional Intraoral Models.

Victim identification following disasters is an important task for the dentist. Use of records of previous dental treatment proved effective in victim identification after the crash of Japan Airlines Flight 123 in 1985. This dental identification procedure can be problematic, however. In exceptional cases, the victim may have had very little or no prior treatment, making identification by this means impossible. The purpose of this study was to establish a new method of dental identification based on morphological comparison of the oral cavity, rather than on evidence of prior dental treatment. This new method involves superimposing 3-dimensional (3-D) models created by digital impression-taking devices, use of which is becoming increasingly widespread in present-day dental treatment. A total of 75 dental models were used to obtain 3-D models. These were then used in a total of 77 superimposition tests. The results demonstrated that the degree of similarity was 98.03－41.30%, and the degree of difference 0.17－29.69%. This indicated that differences among the dental models could be identified with 100% precision. Personal identification by superimposition of such 3-D models offers a useful tool that could compensate for the shortcomings of standard dental identification.

Comparison of Characteristics of Dental Malpractice Trials between Medical Malpractice and Ordinary Divisions in District Courts.

The purpose of this study was to elucidate the characteristics of dental malpractice trials undertaken by medical malpractice divisions and ordinary divisions in district courts. Dentistry disputes in a total of 84 trials held between 1977 and 2014 were investigated. A total of 45 were conducted by medical malpractice divisions, resulting in 18 approvals and 27 dismissals, while 39 were undertaken by ordinary divisions, leading to 24 approvals and 15 dismissals. The parameters analyzed comprised category of dental treatment, judgment, amount claimed, and amount accepted. The results revealed that the mean amount claimed in trials held by medical malpractice divisions (¥12,563,324) was lower than that sought in trials conducted by ordinary divisions. The amount accepted was also found to exceed 50% of the amount claimed in 6 trials held by ordinary divisions (maximum 75.2%), but in only 2 trials conducted by medical malpractice divisions (maximum 54.8%); the mean amount accepted in trials held by medical malpractice divisions was 24.2%. These results indicate that judgments in trials conducted by medical malpractice divisions place a stronger emphasis on resolution of dental malpractice dispute than on pursuing truth or carrying out proper legal procedures.

Population Genetics in Malaysia and Japanese Populations Using Power Plex Y23 System.

Population flow between Southeast Asian countries and Japan continues to gather pace. Accordingly, the number of foreigners involved in incidents in Japan has markedly increased, which means that forensic dentistry is now increasingly being faced with the need to analyze DNA from persons of non-Japanese extraction. The DNA test currently used for personal identification mainly utilizes short tandem repeats (STRs) on autosomal chromosomes and the Y-chromosome. This test was developed for use in personal identification, not for distinguishing among races; nonetheless, the standard method for personal identification is often used because the procedure has been established. To determine the degree to which racial differences can be distinguished by standard DNA analysis, 23 STRs located on the Y chromosome were investigated in 218 Malay and 426 Japanese males. The frequencies of each STR were calculated in the two populations. The difference in the power of discrimination between the Malay and Japanese populations ranged from a minimum of 0.01 to a maximum of 0.27; the difference in polymorphic information content ranged from 0.01 (minimum) to 0.23 (maximum). No major differences were noted in the polymorphisms in these two Mongoloid populations, but the distributions of the 17 STRs differed significantly. Short tandem repeat types demonstrating a likelihood of racial differences were identified in 14 of the STRs. Race-specific STR types were identified in 10 STRs. These results suggest that the likelihood of Malay or Japanese genetic background can be judged based on Y-chromosome STR test results.

Soluble and Planar 2,9-Diazaperopyrenes through Reductive Aromatization of Perylene Diimides: Tunable Emission and Aggregation Behaviors.

Reductive aromatization of perylene diimides with acid anhydrides in the presence of Mn or Zn metals provides soluble and planar 2,9-diazaperopyrenes with ester groups at 1,3,8,10-positions. The pivaloxy groups at the peripheral positions can be transformed into a variety of aryl groups through nickel-catalyzed cross-coupling of ester groups. Emission colors of diazaperopyrenes are tunable by the peripheral substituents. The peripheral substituents also affect the aggregation behaviors of 2,9-diazaperopyrenes in the solution and solid states.

The intervention by an antimicrobial stewardship team can improve clinical and microbiological outcomes of resistant gram-negative bacteria.

Antibiotic stewardship (AS) improves patient outcomes and rates of antibiotic susceptibilities. However, the long-term effect of AS programs (ASPs) on mortality is unclear. This study aimed to assess the impact of bedside interventions by an AS team (AST) on clinical and microbiological outcomes. This retrospective study enrolled patients with bloodstream infections (BSI) and long-term use of broad-spectrum antibiotics (more than 7 days). The main outcomes were 30-day and in-hospital mortality of patients with BSI. The secondary outcomes were the day of therapy (DOT) and susceptibility of antipseudomonal agents. Cases were classified into two groups: the pre-ASP group comprised cases between 2011 and 2013 and the post-ASP group, between 2014 and 2016. The outcomes were then compared between the two groups. Among the patients with all BSI (n = 1187), no significant differences in 30-day mortality were observed between those in the pre-ASP and post-ASP groups. However, in-hospital mortality was significantly lower in the post-ASP group than that in the pre-ASP group (24.8% vs. 18.0%; P = 0.004). Furthermore, the 30-day and in-hospital mortality of resistant gram-negative bacteraemia was significantly lower (20.4% vs.10.5%; P = 0.04 and 28.0% vs.16.1%; P = 0.03). The DOT of broad-spectrum antibiotics decreased except that of tazobactam/piperacillin. The susceptibilities of tazobactam/piperacillin, ceftazidime, cefepime, sulbactam/cefoperazone, gentamicin, ciprofloxacin levofloxacin, imipenem and meropenem were significantly better. Interventions by the AST can improve the clinical and microbiological outcomes, especially resistant gram-negative bacteria. Furthermore, this effect of our ASP can continue for a long term.

Measurement of Linezolid and Its Metabolites PNU-142300 and PNU-142586 in Human Plasma Using Ultra-Performance Liquid Chromatography Method.

An ultra-performance liquid chromatography (UPLC) method was developed and validated for the quantification of linezolid, PNU-142300, and PNU-142586 in human plasma. After protein precipitation using acetonitrile, the protein-free supernatant was separated using reverse-phase chromatography using an ACQUITY UPLC HSS T3 column and monitored at 254 nm. p-Toluic acid was used as the internal standard. No interference peak was observed at the retention times of linezolid, PNU-142300, PNU-142586, and p-toluic acid from blank plasma. The calibration curve of linezolid was linear from 0.2 to 50.0 µg/mL (coefficient of determination (r2) > 0.9999) and those of PNU-142300 and PNU-142586 were linear from 0.2 to 20.0 µg/mL (r2 > 0.9996 and > 0.9998, respectively). The intra- and inter-assay accuracy (%) and precision (relative standard deviation (RSD) %) of the three components were confirmed to meet the criteria of the U.S. Food and Drug Administration guidelines. Tests confirmed the stability of linezolid, PNU-142300, and PNU-142586 in plasma during three freeze-thaw cycles and long-term storage of frozen plasma for up to 30 d; in extracts they were stable in the UPLC autosampler for over 48 h at 4°C. Furthermore, plasma concentrations of linezolid, PNU-142300 and PNU-142586 in patients treated with linezolid could be measured using the UPLC method developed in this study. This assay would be a powerful tool for therapeutic drug monitoring and clinical pharmacokinetic/pharmacodynamic (PK/PD) analyses in the optimization of linezolid treatment.