Favipiravir pharmacokinetics in COVID-19 patients with moderate to severe kidney dysfunction: Lessons learned for future use.

OBJECTIVE: There is limited information on favipiravir pharmacokinetics in critically ill patients and no studies on pharmacokinetics in patients with moderate and severe kidney dysfunction. The aim was to determine favipiravir pharmacokinetics (oral, 1,600 mg, q12h on day 1, then 600 mg, q12h for 4 days) in critically ill COVID-19 patients with kidney dysfunction and to compare those with observations reported in healthy adults. MATERIALS AND METHODS: In a descriptive study, blood samples taken from patients meeting the relevant criteria (estimated glomerular filtration rate < 60 mL/min) were collected and analyzed. Analysis of blood samples was done by high performance liquid chromatography (HPLC), and the maximal concentration (Cmax), the time of maximal concentration (tmax), half-life (T1/2) and area under the curve (AUC0-12h) of favipiravir were calculated (WinNonlin) and compared to reported data in healthy subjects after first administration. RESULTS: Based on analysis of samples collected in 7 patients, the Cmax (29.99 vs. 64.5 µg/mL) of favipiravir was decreased, T1/2 (5.8 vs. 4.8 hours) longer, tmax delayed, while total exposure was lower (AUC0-12: 192.53 vs. 446.09 µg/mL) compared to reported data in healthy subjects after first administration. Exposure remained lower up to day 5. CONCLUSION: In patients with kidney dysfunction related to COVID-19, favipiravir did not reach the expected exposure. This may be due to poorer and delayed absorption, and subsequent altered disposition. Population pharmacokinetic and mechanistic studies are needed to better explore the relevant covariates and to determine the optimal dose in these patients, as this drug is likely of relevance for other indications.

Adapting Fabric Phase Sorptive Extraction as an Innovative Multitool for Sample Transfer and Extraction in Pharmacokinetic Analysis Followed by LC-MS Determination of Levofloxacin in Plasma Samples.

Fabric phase sorptive extraction (FPSE) is a simple microextraction technique that allows analytes to be rescued from matrix components while using a small volume of samples to analyze complex biological systems. This study used FPSE as a microextraction tool and a sample storage and transfer device. Levofloxacin as a model molecule was applied intravenously (IV) to New Zealand male rabbits. The samples were simultaneously extracted by using FPSE and protein precipitation methods. The final solutions were analyzed using LC-MS equipped with an ACE C18 LC Column (150 mm × 4.6 mm, 5 µm) at 25 °C employed in isocratic elution mode using solution A (0.1% formic acid in water)/solution B (0.1% formic acid in acetonitrile) (80:20, v/v). The total analysis time was less than 15 min. The developed method was validated using the ICH M10 bioanalytical method validation and study sample analysis guidelines. The results obtained using FPSE were statistically identical to those obtained using protein precipitation. The plasma samples applied onto FPSE (10 µL onto 1.0 cm × 1.0 cm Biofluid Sampler) were stored in three different temperatures [refrigerator (2-8 °C), at ambient temperature (20 ± 5 °C), and in the stability cabinet (40 °C, 75% humidity)] and three different storage conditions (Eppendorf tubes, plastic containers, and straw paper envelopes). Levofloxacin in plasma samples adsorbed by FPSE biofluid sampler remained stable at 2-8 °C in Eppendorf tubes for at least 1 week. This study showed that FPSE could be used as a sample storage and transfer device for pharmacokinetic applications that need to work with small sample volumes and discard aggressive cold chains to store and transfer the plasma samples.

After the Türkiye Earthquake: The Experience of a Pediatric Emergency Department in a University Hospital Distant from the Disaster Area.

INTRODUCTION: Earthquakes rank among the most deadly natural disasters, and children are particularly affected due to their inherent vulnerability. Following an earthquake, there is a substantial increase in visits to emergency services. These visits stem not only from patients seeking care for physical traumas resulting from the earthquake and its subsequent complications, but also from individuals affected by the circumstances created by the disaster. STUDY OBJECTIVE: This study aims to determine the characteristics and outcomes of children who presented to the pediatric emergency department (PED) after the earthquake and to evaluate children who had crush injuries at a referral tertiary university hospital away from the earthquake area. METHODS: The medical records of children who presented to the PED from the earthquake area from February 6 through March 7, 2023 were retrospectively reviewed. Children rescued from under rubble were categorized as Group 1, those affected by earthquake conditions as Group 2, and patients seeking medical attention due to the follow-up of chronic illnesses were considered as Group 3. Patient data, including sociodemographic characteristics, time period under rubble (TPR), laboratory findings, and details of medical and surgical procedures, developing acute kidney injury (AKI), and the requirement for hemodialysis were recorded. RESULTS: A total of 252 children were enrolled in the study, with 52 (20.6%) in Group 1, 180 (71.4%) in Group 2, and 16 (6.0%) in Group 3. The median age was six (IQR = 1.7-12.1) years. In the first group (n = 52), 46 (85.2%) children experienced crush injuries, 25 children (46.3%) developed crush syndrome, and 14 of them (14/25; 56.0%) required dialysis. In the second group, the most common diagnoses were upper respiratory tract infections (n = 69; 37.9%), acute gastroenteritis (n = 23; 12.6%), simple physical trauma (n = 16; 8.8%), and lower respiratory tract infections (n = 13; 7.1%). For children in the third group, pediatric neurology (n = 5; 33.3%), pediatric oncology (n = 4; 25.0%), and pediatric nephrology (n = 3; 18.8%) were the most frequently referred specialties. CONCLUSION: Crush injuries, crush syndrome, and AKI were the most common problems in the early days following the earthquake. Along with these patients, children who were affected by the environmental conditions caused by the earthquake, as well as children with chronic illnesses, also accounted for a significant portion of visits to the PED, even if they were distant from the disaster area.

Intraoperative arthroscopic classification tool for posterolateral elbow instability.

Background: Introducing and implementing an arthroscopic classification tool for posterolateral elbow instability. Methods: Thirty arthroscopies were performed on 30 patients, and all recordings were collected, blinded, and labeled. Three orthopedic surgeons reviewed and scored all 30 recordings three times with a period of at least seven days in between to analyze the intraobserver and interobserver reliability. The classification consisted of five different grades. Results: Indications for elbow arthroscopy included impingement (n = 7), osteochondritis dissecans (n = 5), pain (n = 7), osteoarthritis (n = 6), and other (n = 5). The kappa value for intrarater reliability was 0.71, indicating good reliability, while the kappa value for inter-rater reliability was 0.38 indicating fair reliability. Conclusion: This new classification is a tool for an arthroscopic assessment of PLRI and can be used as a standardized grading system for further research and communication between orthopedic surgeons. We demonstrated good intrarater reliability (k = 0.71) with fair inter-rater reliability (k = 0.38). However, further research is necessary to study the clinical significance.

Enhancing Oral Bioavailability of Domperidone Maleate: Formulation, In-Vitro Permeability Evaluation, In-Caco-2 cell Monolayers and In-Situ Rat Intestinal Permeability Studies.

BACKGROUND: The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug Delivery System is a novel approach to improve water solubility and, ultimately bioavailability of drugs. OBJECTIVE: This study aimed to develop and characterize new domperidone-loaded self-emulsifying drug delivery systems as an alternative formulation and to evaluate the permeability of domperidone-loaded self-emulsifying drug delivery systems by using Caco-2 cells and via single-pass intestinal perfusion method. METHOD: Three self-emulsifying drug delivery systems were prepared and characterized in terms of pH, viscosity, droplet size, zeta potential, polydispersity index, conductivity, etc. Each formulation underwent 10, 100, 200, and 500 times dilution in intestinal buffer pH 6.8 and stomach buffer pH 1.2, respectively. Female Sprague Dawley rats were employed for in situ single-pass intestinal perfusion investigations. RESULTS: Results of the study revealed that the ideal self-emulsifying drug delivery systems formulation showed narrow droplet size, ideal zeta potential, and no conductivity. Additionally, as compared to the control groups, the optimum formulation had better apparent permeability (12.74 ± 0.02×10-4) from Caco-2 cell monolayer permeability experiments. The study also revealed greater Peff values (2.122 ± 0.892×10-4 cm/s) for the optimal formulation from in situ intestinal perfusion analyses in comparison to control groups (Domperidone; 0.802±0.418×10-4 cm/s). CONCLUSION: To conclude, prepared formulations can be a promising way of oral administration of Biopharmaceutical Classification System Class II drugs.

What Has Changed in Injury-Related Presentations During COVID-19 Pandemic? A Single-Center Experience from a Pediatric Emergency Department.

OBJECTIVE: The coronavirus disease 2019 pandemic affected the healthcare systems worldwide. In this study, we aimed to examine the impact of the coronavirus disease 2019 pandemic on injury-related visits. MATERIALS AND METHODS: We conducted a retrospective analysis of 7648 injury-related pediatric emergency department visits between March 11 and June 30, 2018, 2019, and 2020, and com- pared the total number of visits, triage levels, distributions of injury mechanisms, and admission rates during the pandemic in 2020 to the same period in 2018 and 2019. RESULTS: In the first 4 months of the pandemic, there was a 69.5% drop in all pediatric emer- gency department visits compared to the previous 2 years. Despite this decrease, the propor- tion of injury-related pediatric emergency department visits increased from 14% to 20.9% in 2020 (P < .001). There was a 3.8% increase in the frequencies of patients with high triage acuity levels (T1, T2, and T3) and a 3.8% decrease in patients with low triage acuity levels (P < .001). The domestic injury rate increased from 40% to 60% during the pandemic period (P < .001). Hospitalization rates increased from 6% to 11.5% and admission to intensive care units increased from 0.9% to 3.3%. The differences were statistically significant (P < .001). Visits due to burn increased from 2.7% to 5.2% (P < .001), poisoning from 3.4% to 5.5% (P < .001), bicycle accidents from 3.3% to 6.8% (P < .001), while injuries due to motor vehicle accidents decreased from 2.6% to 1.3% (P = .004) and sports injuries decreased from 8% to 2.1% (P < .001). CONCLUSION: This study revealed that despite the significant decrease in total pediatric emer- gency department visits, percentages of injury-related visits increased during the pandemic.

ltrafiltration-based sample preparation and HPLC-UV determination of diclofenac in human plasma samples.

The sample preparation step is the initial step in pharmaceutical analysis. While ultrafiltration is a well-known technique used in the food and pharmaceutical industries, it has rarely been used to measure the plasma concentration of active pharmaceutical ingredients. This study aimed to analyze diclofenac sodium (DS) in human plasma samples using ultrafiltration-based sample preparation before high-performance liquid chromatography (HPLC) analysis. The advantages and limitations of ultrafiltration-based sample preparation in bioanalysis were evaluated by comparing the results with conventional methods. The precipitating agent was used before ultrafiltration. The analysis was carried on an HPLC-UV system with a C18 column (250 ×4.6 mm, 5 µm) and acetonitrile : phosphate buffer (pH 3.0, 10 mM) (70 : 30 v/v) was used as the mobile phase. The bioanalytical method was validated according to FDA guidelines and applied to spiked samples of DS in commercial human plasma samples. The LOD and LOQ values were 0.006 µg mL-1 and 0.020 µg mL-1, respectively. The method was linear in the range of 0.025-0.50 µgmL-1 with excellent determination coefficients (R2 > 0.9991). The findings of this analysis with low LOD and LOQ values and high recovery values with high trueness and precision proved the matrix minimizing the effect of the presented sample preparation technique.

Determination of the Physicochemical Properties of Piroxicam.

OBJECTIVES: The aim of this study was to determine the acid dissociation constant (pKa) of piroxicam using high performance liquid chromatography (HPLC) and ultraviolet-visible (UV-Vis) spectrophotometry, and to determine the partition coefficient (Log P), distribution coefficient (Log D), and "Log kw" values of piroxicam using HPLC. MATERIALS AND METHODS: The HPLC studies were performed on a reversed-phase ACE C18 (150x4.6 mm ID, 5 µm) column at a flow rate of 1.0 mL min-1. The detector was set to 360 nm. Log D at different pH values (3.0-6.5) was examined with a phosphate buffer (20 mM) and acetonitrile (30:70 v/v) mixture as the mobile phase. For pKa determination, HPLC studies were performed with a mixture of phosphate buffer (20 mM) and methanol within the pH range of 3.50-6.00. Log kw measurements were performed with phosphate buffer (20 mM) and MeOH (from 20:80 v/v to 10:90 v/v) mixtures within the pH range of 3.50-6.00. UV-Vis spectrophotometric pKa measurements were performed at 285 nm wavelength. RESULTS: The pKa value of piroxicam was found to be 5.3 by HPLC and 5.7 by UV-Vis spectrophotometry. Log P of piroxicam was determined as 1.58 in our experimental conditions. Log D values were 1.57, 1.57, 1.44, 1.13, and 0.46 for pH values of 3.17, 3.79, 4.44, 5.42, and 6.56, respectively. CONCLUSION: In the literature, different Log P (3.1, 2.2, and 0.6) and pKa (6.3 and 4.8) values were reported for piroxicam. The Log P (1.58) and pKa (5.3 and 5.7) values obtained for piroxicam in our study were within the range of the literature values. All these results indicate that different experimental approaches used for the determination of physicochemical properties could provide different values. Although UV spectrophotometry is easy to apply, HPLC is a unique technique for simultaneous determination of pKa, Log D, and Log P values of compounds.

Knee arthrodesis for a congenital luxation with Larsen syndrome.

A 31-year-old woman with known Larsen syndrome presented with congenital chronic luxation of her right knee with increasing instability symptoms, which limited her daily activities. We refrained from a constrained knee arthroplasty due to her relatively young age and decided to perform a knee arthrodesis. Knee arthrodesis is a viable lifelong-lasting operative treatment alternative for specific instability-related knee disease. The knee arthrodesis was performed by double plating with an additional fixation of the patella. At 1-yearfollow-up, she was able to walk without limitations and did not experience any pain with complete consolidation of the arthrodesis. At 2-year follow-up, she performed all her daily activities without limitations. Both the Knee injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee subjective knee form (IKDC) improved at 2-year follow-up (KOOS: 61.3; IKDC: 56.3) compared with 1-year follow-up (KOOS: 52; IKDC: 40.2).

Development of a RP-HPLC method for simultaneous determination of reference markers used for in-situ rat intestinal permeability studies.

One of the most common techniques for assessing the intestinal absorption characteristics of drugs is single-pass intestinal perfusion (SPIP) method. Metoprolol tartrate (MT, reference standard) and phenol red (PR, zero permeability marker) are the compounds that are normally used in SPIP studies. The aim of this study was to develop a reverse phase high-performance liquid chromatography (RP-HPLC) method combined with UV-detection for the simultaneous determination of MT and PR in the perfusion medium used in SPIP experiments. Elution was performed using a Restek Raptor C18 column (5 µm, 4.6 mm × 250) at a temperature of 25 °C. The mixture of the mobile phase consisted of (MeOH):(Phosphate buffer solution, PBS), (20 mM, pH 3.0 adjusted with ortho-phosphoric acid),(55:45, v/v). Flow rate and column temperature were set at 1.2 mL min-1 and 25 °C, respectively. MT and PR were injected as 20 µL into the HPLC system. UV detection was performed at 227 nm. The obtained retention times were reported as 2.89 and 3.80 min for MT and PR, respectively. The developed RP-HPLC method was validated according to Q2(R1) guideline of The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The method was linear within the range of 2-50 µg mL-1 for PR and 10-75 µg mL-1 for MT. The developed RP-HPLC method was successfully applied on determination of MT and PR in perfusion medium. The developed method could be helpful for researchers working on in-situ rat intestinal permeability studies and it could be easily modified on further studies.

Nutritional Status of Syrian Refugees in Early Adolescence Living in Turkey.

This study evaluated the nutritional status of Syrian refugees in the early adolescent period living in different vulnerable settings. Nutritional assessment of Syrian refugee adolescents is often neglected but essential for a healthy physical, pubertal and mental development. Growth parameters of Syrian refugee adolescents going to a public school in an urban area and in a temporary protection center (TPC) were recorded along with the Turkish adolescents. Stunting percentages were similar between the groups (p = 0.811). While the proportion of children with a BMI over 85th percentile were significantly higher among Syrian adolescents living in TPC, Turkish children have the highest percentage of underweight (p = 0.01). Both food insecurity and unhealthy weight gain continue to be major concerns for refugee adolescents after their resettlement to a host country. The findings suggest that nutritional assessment and intervention at early adolescence is critical for Syrian refugees depending on their living conditions.

Independent predictive factors for the persistence and tolerance of cow's milk allergy.

BACKGROUND: Cow's milk protein allergy (CMPA) is usually transient, with most children tolerating ingested cow's milk by 3 years of age. This study aimed to determine factors that promote or hindering the development of tolerance to CMPA. METHODS: A logistic regression model was used to determine independent risk factors associated with tolerance and persistence of CMPA. RESULT: A total of 178 children diagnosed with CMPA were included in the study. The patients' median age was 32 months (minimum-maximum, 14 to 144 months), and their median follow-up period was 30 months (minimum-maximum, 12 to 54 months). In the follow-up, CMPA persisted in 62 (34.8%) patients. The patients were divided into 2 groups according to patient's age. Group I was <3 years old and group II was ≥3 years old. The factors independently associated with the persistence of CMPA for group I were as follows: comorbid food allergies (p = 0.021), the presence of an immunoglobulin E (IgE)-mediated reaction (p = 0.001), and respiratory system symptoms (ie, tachypnea) (p = 0.036). The presence of gastrointestinal-related discomfort (p = 0.001) was an independent risk factor associated with the development of tolerance. The presence of comorbid food allergies (p = 0.03) was the only independent predictive factor for CMPA persistence for group II. CONCLUSION: The prognosis in cases of CMPA, a food allergy, is good, with tolerance developing over time. The presence of IgE-mediated CMPA, respiratory-related symptoms (ie, tachypnea), and the presence of comorbid food allergies have negative effects on tolerance.

What Factors Are Associated With Implant Breakage and Revision After Intramedullary Nailing for Femoral Metastases?

BACKGROUND: Actual and impending pathologic fractures of the femur are commonly treated with intramedullary nails because they provide immediate stabilization with a minimally invasive procedure and enable direct weightbearing. However, complications and revision surgery are prevalent, and despite common use, there is limited evidence identifying those factors that are associated with complications. QUESTIONS/PURPOSES: Among patients treated with intramedullary nailing for femoral metastases, we asked the following questions: (1) What is the cumulative incidence of local complications? (2) What is the cumulative incidence of implant breakage and what factors are associated with implant breakage? (3) What is the cumulative incidence of revision surgery and what factors are associated with revision surgery? METHODS: Between January 2000 and December 2015, 245 patients in five centers were treated with intramedullary nails for actual and impending pathologic fractures of the femur caused by bone metastases. During that period, the general indications for intramedullary nailing of femoral metastases were impending fractures of the trochanter region and shaft and actual fractures of the trochanter region if sufficient bone stock remained; nails were used for lesions of the femoral shaft if they were large or if multiple lesions were present. Of those treated with intramedullary nails, 51% (117) were actual fractures and 49% (111) were impending fractures. A total of 60% (128) of this group were women; the mean age was 65 years (range, 29-93 years). After radiologic followup (at 4-8 weeks) with the orthopaedic surgeon, because of the palliative nature of these treatments, subsequent in-person followup was performed by the primary care provider on an as-needed basis (that is, as desired by the patient, without any scheduled visits with the orthopaedic surgeon) throughout each patient's remaining lifetime. However, there was close collaboration between the primary care providers and the orthopaedic team such that orthopaedic complications would be reported. A total of 67% (142 of 212) of the patients died before 1 year, and followup ranged from 0.1 to 175 months (mean, 14.4 months). Competing risk models were used to estimate the cumulative incidence of local complications (including persisting pain, tumor progression, and implant breakage), implant breakage separately, and revision surgery (defined as any reoperation involving the implant other than débridement with implant retention for infection). A cause-specific multivariate Cox regression model was used to estimate the association of factors (fracture type/preoperative radiotherapy and fracture type/use of cement) with implant breakage and revision, respectively. RESULTS: Local complications occurred in 12% (28 of 228) of the patients and 6-month cumulative incidence was 8% (95% confidence interval [CI], 4.7-11.9). Implant breakage occurred in 8% (18 of 228) of the patients and 6-month cumulative incidence was 4% (95% CI, 1.4-6.5). Independent factors associated with increased risk of implant breakage were an actual (as opposed to impending) fracture (cause-specific hazard ratio [HR_cs], 3.61; 95% CI, 1.23-10.53, p = 0.019) and previous radiotherapy (HR_cs, 2.97; 95% CI, 1.13-7.82, p = 0.027). Revisions occurred in 5% (12 of 228) of the patients and 6-month cumulative incidence was 2.2% (95% CI, 0.3-4.1). The presence of an actual fracture was independently associated with a higher risk of revision (HR_cs, 4.17; 95% CI, 0.08-0.82, p = 0.022), and use of cement was independently associated with a lower risk of revision (HR_cs, 0.25; 95% CI, 1.20-14.53, p = 0.025). CONCLUSIONS: The cumulative incidence of local complications, implant breakage, and revisions is low, mostly as a result of the short survival of patients. Based on these results, surgeons should consider use of cement in patients with intramedullary nails with actual fractures and closer followup of patients after actual fractures and preoperative radiotherapy. Future, prospective studies should further analyze the effects of adjuvant therapies and surgery-related factors on the risk of implant breakage and revisions. LEVEL OF EVIDENCE: Level III, therapeutic study.

Genetic Variants and Anterior Cruciate Ligament Rupture: A Systematic Review.

BACKGROUND: Studies have shown a familial predisposition for anterior cruciate ligament (ACL) rupture and have been followed by genetic-association studies on polymorphisms in candidate genes in recent years. To date, no systematic review with a best-evidence synthesis has evaluated the influence of genetics on this devastating knee injury. OBJECTIVE: Our objective was to evaluate the association between genetic variants and ACL rupture. METHODS: We performed an extensive search in Embase, MEDLINE, Web of Science, Scopus, PubMed Publisher, Cochrane Register of Clinical Trials, and Google scholar up to 24 August 2015. Studies were eligible if they met the following inclusion criteria: (1) design was a case-control study, retrospective or prospective follow-up study, or a randomized controlled trial (RCT); (2) the study examined the association between a genetic variant and ACL rupture in both an ACL and a control group. We determined the risk of bias for all included studies. RESULTS: We included a total of 16 studies (eight at high risk of bias and eight with an unclear risk) that examined 33 different DNA variants. Conflicting evidence was found for the COL1A1 rs1800012 and COL3A1 rs1800255 variants, whereas limited evidence was found for no association of the COL5A1 rs12722 and rs13946 and COL12A1 rs970547 variants (all encoding collagen). Evidence was insufficient to draw conclusions as to whether any other genetic variant identified in this review had any association with ACL rupture. CONCLUSIONS: More research is needed to support a clear association between ACL rupture and genetic variants. Genome-wide studies are recommended for exploring more potential genetic variants. Moreover, large prospective studies are needed to draw robust conclusions.

Effect of permeability enhancers on paracellular permeability of acyclovir.

OBJECTIVES: According to Biopharmaceutics Classification System (BCS), acyclovir is a class III (high solubility, low permeability) compound, and it is transported through paracellular route by passive diffusion. The aim of this study was to investigate the effect of various pharmaceutical excipients on the intestinal permeability of acyclovir. METHODS: The single-pass in-situ intestinal perfusion (SPIP) method was used to estimate the permeability values of acyclovir and metoprolol across different intestinal segments (jejunum, ileum and colon). Permeability coefficient (Peff ) of acyclovir was determined in the absence and presence of a permeation enhancer such as dimethyl ß-cyclodextrin (DM-ß-CD), sodium lauryl sulfate (SLS), sodium caprate (Cap-Na) and chitosan chloride. KEY FINDINGS: All enhancers increased the permeability of paracellularly transported acyclovir. Although Cap-Na has the highest permeability-enhancing effect in all segments, permeation-enhancing effect of chitosan and SLS was only significant in ileum. On the other hand, DM-ß-CD slightly decreased the permeability in all intestinal segments. CONCLUSIONS: These findings have potential implication concerning the enhancement of absorption of paracellularly transported compounds with limited oral bioavailability. In the case of acyclovir, Cap-Na either alone or in combination with SLS or chitosan has the potential to improve its absorption and bioavailability and has yet to be explored.

Prevention of pre-harvest aflatoxin production and the effect of different harvest times on peanut (Arachis hypogaea L.) fatty acids.

The aim of this study was to investigate the relationship between aflatoxin and fatty acids and to determine the optimum harvest time to avoid pre-harvest aflatoxin formation. It was established that harvest time had statistically significant effects on the levels of saturated fatty acids: myristic acid (C14:0), palmitic acid (C16:0), heptadecanoic acid (C17:0), stearic acid (C18:0), arachidic acid (C20:0), behenic acid (C22:0), lignoceric acid (C24:0), monounsaturated fatty acids; palmitoleic acid (C16:1), heptadecenoic acid (C17:1), oleic acid (C18:1) and gadoleic acid (C20:1); and on polyunsaturated fatty acids: linoleic acid (C18:2) and linolenic acid (C18:3). By delaying the harvest time, the ratio of saturated fatty acids decreased and unsaturated fatty acids increased. It was shown that the longer harvesting was delayed, the greater the quantity of oleic acid that was produced. Before harvest time, if the soil moisture was 5% or higher, aflatoxin was produced by fungi. It was found that the weather conditions of the region were suitable for aflatoxin production. Soil moisture appears to be more important than soil temperature for aflatoxin formation. The production of aflatoxin was not observed in the first and second harvests, both of which are at early harvest times. It was found that aflatoxin B1 during harvest time was the most significant of the four toxins. The third harvest time, which is the most widely used, was observed to have significant problems due to aflatoxin formation. Therefore, it is suggested as a result of this study that the harvest of peanuts must be done considering seed yield before the middle of September to avoid aflatoxin formation at harvest time.

HPLC method development for the simultaneous analysis of amlodipine and valsartan in combined dosage forms and in vitro dissolution studies

A simple, rapid and reproducible HPLC method was developed for the simultaneous determination of amlodipine and valsartan in their combined dosage forms, and for drug dissolution studies. A C18 column (ODS 2, 10 μm, 200 x 4.6 mm) and a mobile phase of phosphate buffer (pH 3.6 , 0.01 mol L-1):acetonitrile: methanol (46:44:10 v/v/v) mixture were used for separation and quantification. Analyses were run at a flow-rate of 1 mL min-1 and at ambient temperature. The injection volume was 20 μL and the ultraviolet detector was set at 240 nm. Under these conditions, amlodipine and valsartan were eluted at 7.1 min and 3.4 min, respectively. Total run time was shorter than 9 min. The developed method was validated according to the literature and found to be linear within the range 0.1 - 50 μg mL-1 for amlodipine, and 0.05 - 50 μg mL-1 for valsartan. The developed method was applied successfully for quality control assay of amlodipine and valsartan in their combination drug product and in vitro dissolution studies.

Desenvolveu-se método de HPLC rápido e reprodutível para a determinação simultânea de anlodipino e valsartana em suas formas de associação e para os estudos de dissolução dos fármacos. Utilizaram-se coluna C18 (ODS 2, 10 μm, 200 x 4,6 mm) e fase móvel tampão fosfato (pH 3,6, 0,01 mol L-1):acetonitrila: metanol para a separação e a quantificação. As análises foram efetuadas com velocidade de fluxo de 1 mL min-1 e à temparatura ambiente O volume de injeção foi de 20 μL e utilizou-se detector de ultravioleta a 240 nm. Sob essas condições, anlodipino e valsartana foram eluídas a 7,1 min e 3,4 min, respectivamente. O tempo total de corrida foi menor que 9 min. O método desenvolvido foi validado de acordo com a literatura e se mostrou linear na faixa de 0,1-50 μg mL-1 para anlodipino e de 0,05-50 μg mL-1 para valsartana. O método desenvolvido foi aplicado com sucesso para ensaios de controle de qualidade de associações de anlodipino e valsartana e nos estudos de dissolução in vitro.