Shoulder muscle weakness and proprioceptive impairments in type 2 diabetes mellitus: exploring correlations for improved clinical management.

Background: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder with systemic implications, potentially affecting musculoskeletal health. This study aimed to assess shoulder muscle strength and joint repositioning accuracy in individuals with T2DM, exploring potential correlations and shedding light on the musculoskeletal consequences of the condition. The objectives were two-fold: (1) to assess and compare shoulder strength and joint repositioning accuracy between individuals with T2DM and asymptomatic counterparts, and (2) to examine the correlation between shoulder strength and joint repositioning accuracy in individuals with T2DM. Methods: A cross-sectional study enrolled 172 participants using the convenience sampling method, including 86 individuals with T2DM and an age-matched asymptomatic group (n = 86). Shoulder strength was assessed using a handheld dynamometer, while joint repositioning accuracy was evaluated with an electronic digital inclinometer. Results: Individuals with T2DM exhibited reduced shoulder muscle strength compared to asymptomatic individuals (p < 0.001). Additionally, joint repositioning accuracy was significantly lower in the T2DM group (p < 0.001). Negative correlations were observed between shoulder strength and joint repositioning accuracy in various directions (ranging from -0.29 to -0.46, p < 0.001), indicating that higher muscle strength was associated with improved joint repositioning accuracy in individuals with T2DM. Conclusion: This study highlights the significant impact of T2DM on shoulder muscle strength and joint repositioning accuracy. Reduced strength and impaired accuracy are evident in individuals with T2DM, emphasizing the importance of addressing musculoskeletal aspects in diabetes management. The negative correlations suggest that enhancing shoulder muscle strength may lead to improved joint repositioning accuracy, potentially contributing to enhanced physical functioning in this population.

Cervical Health Parameters in Car Drivers: Assessing the Influence of Driving on Neck Pain, Mobility, Proprioception and Craniovertebral Angle - A Cross-Sectional Study.

Purpose: Prolonged sitting during driving is linked to neck pain, uncomfortable body positions, and repetitive motions. Recognizing these challenges, this study aimed to investigate Cervical Health Parameters in Car Drivers. Methods: The sample consisted of 160 car drivers between 25 and 45 years. This subject was then divided into two groups based on neck pain. Participants met the required criteria, such as being between 25-45 years of age, maintaining a BMI of 18-24, and driving for at least 2 hours each day for at least 3-5 years. To evaluate the results, we employed a clinometer and compass app on a smartphone to measure the Cervical Range of Motion (CROM). We used Surgimap software to estimate the Craniovertebral Angle (CVA), and a (Cervical range of motion) CROM device was used for proprioception assessment. Results: The result shows the participants in neck pain group displayed lower Cervical Range of Motion (CROM) values than without neck Pain Group. Similarly, the Craniovertebral Angle (CVA) was smaller in the neck Pain Group (mean difference of -6.3°), indicating a more forward head posture. Neck pain resulted in a mean difference of -4.5° in proprioception accuracy. This indicates that neck pain affects CROM, CVA, and proprioception in car drivers. Conclusion: Car driving significantly impacts cervical parameters in individuals with neck pain, reducing cervical range of motion, altered craniovertebral angle, and diminished proprioceptive accuracy. These findings emphasize the need for ergonomic interventions and proprioceptive training tailored for drivers. Future research should broaden demographic parameters and consider potential confounders to provide a holistic understanding of the relationship between car driving and neck health.

The Effects of Six Weeks Pulmonary Rehabilitation on Functional and Psychological Outcomes in Long-COVID Patients: Preliminary Results from Serbian Single Center Study.

Background and Objectives: In this study, we aimed to evaluate the effects of six weeks of pulmonary rehabilitation on functional and psychological outcomes in long-COVID patients. Material and Methods: The prospective clinical study included 46 patients that were diagnosed with COVID-19. A respiratory rehabilitation program was implemented for six weeks. Further valuables were tested before the beginning of the rehabilitation program (admission) and six weeks after (discharge): SpO2, heart rate, respiratory rate, Visual Analogue Scale (VAS) score, Borg score, Sit-to-Stand (StS) test number of repetition, distance of 6-Minute Walking Test (6MWT), Patient Health Questionnaire (PHQ) 9 score and Generalized anxiety disorder (GAD) anxiety score. These parameters were tested before the rehabilitation program on admission and at discharge and after the rehabilitation program on admission and at discharge. The results were presented with standard descriptive and analytical methods. Differences between the continuous variables before and after physical rehabilitation intervention were tested using the Wilcoxon test. Graphical analysis is presented with a box plot. Results: On discharge, in comparison with admission, the values of SpO2 were significantly lower (p = 0.007) before the 6MWT, and VAS scores were significantly higher (p = 0.036), while after the 6MWT, VAS scores were significantly lower (p < 0.001) as were Borg scores (p = 0.016). On discharge, in comparison with admission, the respiratory rate was significantly higher (p = 0.005) before the StS test, and Borg scores were significantly lower (p = 0.001), while after the StS test, SpO2 levels were significantly higher (p = 0.036) and VAS scores were significantly lower (p < 0.001), as were Borg scores (p = 0.008). After discharge, the values of the StS test were significantly higher (p = 0.011), PHQ9 scores were significantly lower (p < 0.001) and GAD anxiety scores were significantly lower as well (p = 0.005), while the distances measured in meters on the 6MWT were significantly increased (p < 0.001). Conclusions: A structured rehabilitation program in our study was shown to have beneficial effects on physiological, psychological and functional improvements in patients with long-COVID, and therefore it is advisable for these patients.

Efficacy of Core-Strengthening and Intensive Dynamic Back Exercises on Pain, Core Muscle Endurance, and Functional Disability in Patients with Chronic Non-Specific Low Back Pain: A Randomized Comparative Study.

BACKGROUND: Chronic back pains are progressively disabling working individuals, including 60-80% of the general population, for which their diagnosis is challenging to healthcare workers worldwide, thereby becoming a burden to nations. PURPOSE: The study aimed to investigate the efficacy of core strengthening exercise (CSE) and intensive dynamic back exercise (IDBE) on pain, core muscle endurance, and functional disability in patients with chronic non-specific low back pain (LBP). METHODS: The study was based on a three-arm parallel-group randomized control design. Forty-five participants with chronic non-specific LBP were recruited and randomly divided into the CSE, IDBE, and Control groups. The CSE and IDBE groups received CSE and IDBE, respectively. However, the Control group received no intervention. Numeric pain rating scale, Oswestry Disability Index, core flexors, extensors, and side bridge tests assessed pain intensity, functional disability, and endurance of core muscles. Outcome scores for the dependent variables were collected at baseline (pre-intervention) and six-week post-intervention. There were no follow-up measurements in this study. A one-way multivariate analysis of covariance (MANCOVA) was used to analyze the intervention effects on the outcomes within groups and between groups, respectively; keeping the significance-level alpha at 95%, i.e., p < 0.05. A univariate F-test was performed to observe the superiority of one treatment over another. Pearson's correlation coefficient test was conducted to determine a relation between the dependent variables. In all statistical analyses, the level of significance α was kept at 0.05. RESULTS: All forty-five out of sixty-three participants with chronic non-specific low back pain (male, 32 and female, 23; average age, 20.24 ± 1.46 years; average pain duration, 19.6 ± 5.42 weeks) completed the study and their data were analyzed. The MANCOVA test showed a significant difference between the treatment groups on the combined multiple endurance tests for the core muscles (flexors, extensors, side bridge tests to the right and left), Visual Analog Scale (VAS), and Oswestry Disability Index (ODI) scores after controlling for baseline scores of all the dependent variables: F (6, 12) = 23.381; p < 0.05; Wilks' Λ = 0.033; partial η2 = 0.819. A post hoc pair-wise comparison followed by a univariate F-test indicated that a significant improvement was found between the CSE vs. IDBE vs. Control groups on the post-test scores of all the dependent variables except VAS and EET (CSE vs. IDBE only). A Pearson's correlation coefficient test revealed a notable relation between the dependent variables. CONCLUSIONS: The experimental group CSE was found to be more effective than IDBE on improving functional disability, cores' flexors, and side bridges' endurance tests than IDBE. The magnitude of this improvement exceeded the minimal clinically important difference (MCID), suggesting a clinically relevant enhancement in functional disability, core flexors, and side bridge endurance for participants engaged in CSE. However, CSE vs. IDBE revealed non-significant differences on reducing pain and core extensors' endurance. The absence of statistically significant differences suggests that the observed changes did not exceed the established MCID for pain intensity and core extensors' endurance. In addition, partial eta-squared value revealed the superiority of CSE over IDBE and Control groups. This suggests that the observed differences between the two interventions are not only statistically significant, but also clinically relevant, surpassing the established MCID.

Exploring the Nexus of lower extremity proprioception and postural stability in older adults with osteoporosis: a cross-sectional investigation.

Background: Osteoporosis, characterized by reduced bone mass and micro-architectural deterioration, poses a significant public health concern due to increased fracture susceptibility. Beyond bone health, this cross-sectional study aimed to assess and compare lower extremity proprioception and postural stability in individuals with and without osteoporosis and to explore their correlation within the osteoporosis group. Method: In this prospective cross-sectional study, 80 participants were divided into two groups: osteoporosis (n = 40) and control (n = 40). The demographic characteristics and clinical parameters of the participants were as follows: Age (years) - Osteoporosis group: 65.04 ± 4.33, Control group: 65.24 ± 4.63; Sex (%) - Osteoporosis group: Male 30%, Female 70%; Control group: Male 30%, Female 70%; Body mass index (kg/m2) - Osteoporosis group: 23.7 ± 3.2, Control group: 24.5 ± 4.6; T-score (Lumbar) - Osteoporosis group: -2.86 ± 1.23, Control group: 0.27 ± 0.58; T-score (hip) - Osteoporosis group: -2.28 ± 0.79, Control group: 0.68 ± 0.86. Joint Position Sense (JPS) at the hip, knee, and ankle was assessed using a digital inclinometer, and postural stability was measured using computerized force platforms. Result: Osteoporosis participants exhibited higher errors in hip (5.63° vs. 2.36°), knee (4.86° vs. 1.98°), and ankle (4.46° vs. 2.02°) JPS compared to controls. Postural stability measures showed increased anterior-posterior sway (10.86 mm vs. 3.98 mm), medial-lateral sway (8.67 mm vs. 2.89 mm), and ellipse area (966.88 mm2 vs. 446.19 mm2) in osteoporosis participants. Furthermore, correlation analyses within the osteoporosis group unveiled significant positive associations between lower extremity proprioception and postural stability. Specifically, hip JPS exhibited a strong positive correlation with anterior-posterior sway (r = 0.493, p = 0.003), medial-lateral sway (r = 0.485, p = 0.003), and ellipse area (r = 0.496, p < 0.001). Knee JPS displayed a moderate positive correlation with anterior-posterior sway (r = 0.397, p = 0.012), medial-lateral sway (r = 0.337, p = 0.032), and ellipse area (r = 0.378, p < 0.001). Similarly, ankle JPS showed a moderate positive correlation with anterior-posterior sway (r = 0.373, p = 0.023), medial-lateral sway (r = 0.308, p = 0.045), and ellipse area (r = 0.368, p = 0.021). Conclusion: These findings underscore the interplay between proprioceptive deficits, compromised postural stability, and osteoporosis, emphasizing the need for targeted interventions to improve fall prevention strategies and enhance the quality of life for individuals with osteoporosis.

Prediction of geomechanical bearing capacity using autoregressive deep neural network in carbon capture and storage systems.

Carbon Capture and Storage (CCS) field is growing rapidly as a means to mitigate the accumulation of greenhouse gas emissions. However, the geomechanical stability of CCS systems, particularly related to bearing capacity, remains a critical challenge that requires accurate prediction models. In this research paper, we investigate the efficacy of employing an Autoregressive Deep Neural Network (ARDNN) algorithm to predict the geomechanical bearing capacity in CCS systems through shear wave velocity prediction as an index for bearing capacity evaluation of deep rock formations. The model utilizes a dataset consisting of 23,000 data points to train and test the ARDNN algorithm. Its scalability, use of deep learning techniques, automatic feature extraction, adaptability to changes in data, and versatility in various prediction tasks make it an attractive option for accurate predictions. The results demonstrate exceptional performance, as evidenced by an R-squared value of 0.9906 and a mean squared error of 0.0438 for the test data compared to the measured data. This research has significant practical implications for effectively predicting geomechanical stability in CCS systems, thus mitigating potential risks associated with their operation.

Exploring the Interplay of Muscular Endurance, Functional Balance, and Limits of Stability: A Comparative Study in Individuals with Lumbar Spondylosis Using a Computerized Stabilometric Force Platform.

Lumbar spondylosis, characterized by degenerative changes in the lumbar spine, often leads to pain, reduced spinal stability, and musculoskeletal dysfunction. Understanding the impact of lumbar spondylosis on musculoskeletal function, particularly lumbar extensor endurance, functional balance, and limits of stability, is crucial for improving the management and well-being of affected individuals. This study aimed to assess lumbar extensor endurance, functional balance, and limits of stability in individuals with lumbar spondylosis compared to age-matched healthy individuals and explore the correlations among these parameters within the lumbar spondylosis group. The lumbar spondylosis group consisted of 60 individuals initially screened by an orthopedician and referred to physical therapy. Age-matched healthy controls (n = 60) were recruited. Inclusion criteria encompassed adults aged 45-70 years for both groups. Lumbar extensor endurance was assessed using the Sorensen test, functional balance with the Berg Balance Scale, and limits of stability using a computerized stabilometric force platform. Lumbar extensor endurance was significantly lower in individuals with lumbar spondylosis compared to healthy controls (23.06 s vs. 52.45 s, p < 0.001). Functional balance, as assessed by the Berg Balance Scale, demonstrated a significant decrement in the lumbar spondylosis group (48.36 vs. 53.34, p < 0.001). Additionally, limits of stability variables, under both eyes-open and eyes-closed conditions, exhibited marked impairments in the lumbar spondylosis group (p < 0.001 for all variables). Within the lumbar spondylosis group, lumbar extensor endurance exhibited significant positive correlations with functional balance (0.46, p < 0.001) and negative correlations with limits of stability variables (r ranging from -0.38 to -0.49, p < 0.01 for all variables). This study underscores the significance of addressing lumbar extensor endurance, functional balance, and stability impairments in the comprehensive management of lumbar spondylosis.

Neuronal Cell Types in the Spinal Trigeminal Nucleus of the Camel Brain.

Neurons in the spinal trigeminal nucleus of a camel were morphologically studied by the Golgi impregnation method. The neurons were classified based on the size and shape of their cell bodies, the density of their dendritic trees, and the morphology and distribution of their appendages. At least 12 morphological types of neurons were found in the camel spinal trigeminal nucleus, including the following: stalked, islets, octopus-like, lobulated, boat-like, pyramidal, multipolar, round, oval, and elongated neurons. These neurons exhibited large numbers of various forms of appendages that arise not only from their dendrites but also from their cell bodies. Moreover, neurons with unique large dilatations especially at their dendritic branching points were also reported. The neurons reported in this study displayed an array of different sizes and shapes and featured various forms of appendages arising from cell bodies and dendrites. Such morphologically distinctive neuronal cell types might indicate an evolutionary adaptation to pain and temperature processing pathways at the level of the spinal trigeminal nucleus in camels, which traditionally live in a very harsh climatic environment and are frequently exposed to painful stimuli.

Efficacy of cervical mobilization with post-isometric relaxation in managing mechanical neck pain, ROM, and functional limitations associated with myofascial trigger points.

BACKGROUND: Sedentary lifestyle, age-related degenerative changes or traumatic injuries leads to cervical spine structural mal-alignment, which results in neck pain and other symptoms. Various therapeutic exercises and manual techniques have been proven to be beneficial in terms of managing these symptoms. This study aimed to determine the combined effects of cervical mobilization and post-isometric relaxation (PIR) technique on managing neck pain, cervical side flexion range of motion, and functional limitation in participants with mechanical neck pain linked with myofascial trigger points. METHODS: This study followed a 2-arm, parallel-group, pretest-posttest randomized comparative design. Thirty participants with mechanical neck pain associated with myofascial trigger points aged 30.87 ±â€…4.45 years were randomly allocated to Groups 1 and 2. Group 1 received conventional intervention, PIR, and cervical mobilization techniques while Group 2 received conventional intervention and PIR technique only. Neck pain, muscle tenderness, cervical range of motion, and functional limitations were assessed using a visual analog scale, pressure pain threshold (PPT), goniometer, and neck disability index (NDI) questionnaire, respectively at baseline on day 1 and post-intervention on day 7, 14, and 21. Wilcoxon signed-rank test and the Mann-Whitney U test evaluated within-group and between-group analyses, respectively. Statistical significance was established at a 95% confidence interval, indicated by P < .05. RESULTS: Significant differences (95% confidence interval [CI], P < .05) were observed within each group for all the outcomes scores when compared to the baselines across multiple time points. Significant variations were observed between the groups when comparing visual analog scale and NDI scores at weeks 1, 2, and 3 post-interventions. In contrast, insignificant differences (95% CI, P > .05) were observed for side flexion range of motion and PPT compared at weeks 1, 2, and 3 post-interventions except for PPT at week 3 post-intervention (95% CI, P < .05). Additionally, Cohen d test revealed the superiority of group 1 over group 2 in reducing pain and functional limitations and improving cervical side flexion range of motion and PPT. CONCLUSION: The combination of cervical mobilization and Post-isometric relaxation techniques was discovered to effectively alleviate neck pain and enhance functional abilities when contrasted with the application of post-isometric relaxation alone in patients with mechanical neck pain linked with myofascial trigger points.

Small Bowel Injury During Peritoneal Entry at Cesarean Section: A Five-Year Case Series.

Introduction Small bowel injury during peritoneal entry may occur unexpectedly at cesarean section (CS) and may present unexpected management problems and prolonged postoperative hospital stay. Methods This was an observational study of patients who sustained inadvertent injuries compared to those who did not. Both study and control patients had the same number of previous cesarean sections. Findings In this study population, the frequency of small bowel injury during peritoneal entry was 0.0003/10,000 cesarean sections. The majority comprised serosal trauma (7/10) and tended to occur in females who had had two or more CS. Compared to patients with a similar number of previous cesarean sections, patients who sustained small bowel injuries in the index cesarean section were twice as likely to have had adhesiolysis of flimsy or dense lesions in the immediate preceding procedure. Conclusion Bowel injury during peritoneal entry at cesarean section is rare but may be frequently encountered in maternity units with high-volume CS rates.

A Golgi study of neurons in the camel cerebellum (Camelus dromedarius).

Neurons in the cerebellar cortex of camels were studied using modified Golgi impregnation methods. Neurons were classified according to their position, morphology of their soma, density and distribution of dendrites, and the course of their axons. Accordingly, eight types of neurons were identified. Three types were found in the molecular layer: upper and lower stellate cells and basket cells, and four types were found in the granular layer: granule cells, Golgi Type II cells, Lugaro cells, and unipolar brush cells. Only the somata of Purkinje cells were found in the Purkinje cell layer. The molecular layer is characterized by the presence of more dendrites, dendritic spines, and transverse fibers. Golgi cells also show extensive dendritic branching and spines. The results illustrate the neuronal features of the camel cerebellum as a large mammal living in harsh environmental conditions. These findings should contribute to advancing our understanding of species-comparative anatomy in achieving better coordination of motor activity.

Neuronal cell types in the anterior ventral thalamic nucleus of the camel.

The anterior ventral nucleus neurons in of the camel brain were morphologically studied by Golgi impregnation method. Two neuronal types of were found in the camel anterior ventral thalamic nucleus, namely, Golgi-type I neurons and Golgi-type II neurons. Those neurons were generally similar to their counterparts in the human thalamus. The Golgi-type I neurons exhibited medium to large cell body (mean diameter = 25 µm) which was either multipolar or triangular in shape. They had from 3 to 10 primary dendrites with many branches but with no spines or appendages. The Golgi-type II neurons had small to medium size (somatic mean diameter = 17.5 µm), their cell bodies were variable in shape, some were round, and others were multipolar or fusiform. These cells bodies had two to six primary dendrites with few branches that may have spines and/or grape-like appendages. Our findings shed some light on the anterior ventral thalamic nucleus structure of the camel as one of the strongest adaptive mammals to the hard climatic conditions.

A Golgi study of the camel cuneate nucleus.

Neurons in the cuneate nucleus of the camel brain stem were studied by Golgi method. Six types of neurons were identified based on soma size and shape, density of dendritic trees, morphology and distribution of spines, and appendages. Type I neurons had large spherical somata with somatic appendages. Dendritic appendages were predominant on proximal dendrites with terminal flower-like appendages. Type II neurons had medium to large soma. Appendages and spines were found for the soma as well as along dendrites of different orders. Axons with local branches were seen for these neurons. Type III neurons were small to medium spheroidal or triangulated with large number of spines and appendages on all parts of neurons including soma, dendrites, and initial axonal segments. Axons of these neurons branch profusely and formed rich local axonal arborizations. Type IV medium-size neurons have bipolar, round, or fusiform soma with somatic spines. Their dendrites were sparsely branching with spines and terminal side branches. Type V neurons were spheroid or triangular with small soma with somatic appendages. Their dendrites were sparsely branching and terminate as thin spiny side branches. Type VI neurons were small-size unipolar, round, or fusiform with some dendritic spines and protrusions. These findings shed some light on the structure of the cuneate nucleus of one of the largest animals (the camel).

Recommendations on: internal standard criteria, stability, incurred sample reanalysis and recent 483s by the Global CRO Council for Bioanalysis.

"The Global CRO Council (GCC) for Bioanalysis was formed in an effort to bring together many CRO leaders to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry"

Two-way crossover bioequivalence study of alendronate sodium tablets in healthy, non-smoking male volunteers under fasted conditions.

This study was conducted in order to assess the bioequivalence of two different formulations containing 70 mg alendronate sodium (CAS 121268-17-5) under fasted conditions. One hundred twenty-two healthy male volunteers were enrolled in an open label, randomized, crossover design with a wash-out period of 20 days in one study center. Urine samples were collected up to 36 h post-dose, and the concentrations of alendronic acid were determined using a high performance liquid chromatographic method with pre-derivatization and fluorescence detection (HPLC/FL) method. The mean Ae(0-t) were 604.24 +/- 348.73 microg and 627.36 +/- 327.99 microg, while the mean R(max) were 193.87 +/- 114.68 microg/h and 202.00 +/- 107.83 microg/h for the test and reference formulations, respectively. The T(max) of the test and reference tablets were 1.26 +/- 0.58 h and 1.26 +/- 0.51 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90% confidence intervals for the primary target parameters, intra-individual ratios for Ae(0-t) and R(max) of alendronic acid, were between 0.86-1.00 and 0.85-1.01, respectively, and thus within the acceptance range for bioequivalence criteria. In the light of the present study it can be concluded that the test formulation is bioequivalent to the reference formulation.

Bioanalytical method development and validation using incurred samples--simultaneous quantitation of ramipril and ramiprilat in human EDTA plasma by LC-MS/MS.

A new method development and validation approach is proposed in order to develop a reliable method for the simultaneous quantitation of ramipril and ramiprilat in the presence of numerous labile metabolites. This new approach involves the usage of a synthesized labile acyl glucuronide of ramipril as well as individual and pooled incurred (study) samples in the development and validation process. Following the method validation and prior to its application to a large clinical study, a mini pilot study was performed to evaluate the performance of the method. When the samples from the mini pilot study were analyzed by two different scientists, 100% of the results from incurred sample reanalysis (ISR) matched within 8% of difference and the mean differences were 0.21% and 1.40% for ramipril and ramiprilat, respectively. The validated concentration range reported in this article is 0.2-80 ng/mL for both analytes. Various stabilities, such as bench-top, autosampler, freeze/thaw, and long-term, were also successfully evaluated. The key to the success were low sample processing temperature (4 degrees C), proper choice of sample extraction procedure, and adequate chromatographic conditions to obtain good peak shape without the need of derivatization and baseline separation between the analytes and their glucuronide metabolites.

Internal standard response variations during incurred sample analysis by LC-MS/MS: Case by case trouble-shooting.

Internal standard (IS) responses can directly impact the accuracy of reported concentrations in bioanalysis as the majority of LC-MS/MS methods are based on analyte/IS response ratios for quantitation. Due to the complexity of incurred sample matrices and drug formulation, variable IS responses are quite common upon applying a validated method to the analysis of incurred samples. To maintain the integrity of a study and to avoid economic losses, it is therefore extremely important to monitor IS response variations during bioanalysis and to quickly identify the root causes if variations are observed. Presented in this article are twelve trouble-shooting examples from the analyses of incurred samples by a wide variety of bioanalytical methods, including human error, malfunctioning equipment/instruments, wrong material, matrix effect and inherent issues with a bioanalytical method. Insightful ideas for how to trouble-shoot and how to develop more reliable bioanalytical methods can be drawn from these practical examples.

Automated liquid-liquid extraction method for high-throughput analysis of rosuvastatin in human EDTA K2 plasma by LC-MS/MS.

BACKGROUND: Liquid-liquid extraction has been widely used for the analysis of rosuvastatin due to its many attractive features, such as low cost and clean extract. However, manual transfer of the organic phase poses a challenge, particularly when a batch size is large. To overcome the challenge, a simple automated high-throughput (192 samples per batch) liquid-liquid extraction method with short (3.0-min) chromatographic run time was proposed. Rosuvastatin was separated using a gradient on a reversed-phase C18 column and detected in the multiple reaction monitoring made with a mass transition of m/z 482.3→258.2 amu. RESULTS: The assay exhibited a linear range from 50 to 25000 pg/ml (r ≥ 0.9976). The intra- and inter-day accuracy ranged from 98.16 to 103.84% and 101.18 to 103.95%, respectively. The intra- and inter-day precision ranged from 0.70 to 6.17% and 2.19 to 5.07%, respectively. CONCLUSION: Finally, the validated method was successfully applied to bioequivalence studies.

The 2nd Calibration and Validation Group workshop on recent issues in good laboratory practice bioanalysis.

This event was organized by the Calibration and Validation Group (a scientific nonprofit organization based in Toronto, Canada) as a 1.5-day workshop for contract research organizations and pharmaceutical companies involved in providing bioanalytical data for bioavailability, bioequivalence, pharmacokinetic and comparability studies.

Bioequivalence studies of tacrolimus capsule under fasting and fed conditions in healthy male and female subjects.

The bioequivalence of tacrolimus (CAS 104987-11-3) 5 mg capsules was assessed in two single-dose, open-label, randomIzed 2-way crossover trials with a minimum washout period of 14 days; one trial was conducted under fasting condition (n = 44) and the other one under fed condition (n = 48). Blood samples were collected over a 120-h period and concentrations were assayed using a liquid chromatography tandem mass spectrometry (LCMS/MS) method. A non-compartmental method was used for calculation of pharmacokinetic parameters. Under fasting conditions, mean AUC(0-t), AUC(0-inf) and C(max) were comparable between the test (296 ng x h/mL, 318 ng x h/mL and 32 ng/ mL, respectively) and the reference formulations (289 ng x h/mL, 309 ng x h/mL and 33 ng/mL, respectively). T(max) was reached between 1.5 and 2 h post-dose. Mean AUC(0-t), AUC(0-inf) and C(max) were also comparable under fed conditions (154 ng x h/mL, 169 ng x h/mL and 7.6 ng/mL, respectively, for the test and 161 ng x h/mL, 176 ng x h/mL and 7.5 ng/mL, respectively, for the reference formulation). Under fed conditions, T(max) was reached between 5 and 6 h post-dose. 90% geometric confidence intervals were all within the acceptable 80-125% limit, suggesting bioequivalence between the generic product and the innovator product.