Tolerance Intervals Research Articles

Methods and reference data for middle ear transfer functions

Human temporal bone specimens are used in experiments measuring the sound transfer of the middle ear, which is the standard method used in the development of active and passive middle ear implants. Statistical analyses of these experiments usually require that the TB samples are representative of the population of non-pathological middle ears. Specifically, this means that the specimens must be mechanically well-characterized. We present an in-depth statistical analysis of 478 data sets of middle ear transfer functions (METFs) from different laboratories. The data sets are preprocessed and various contributions to the variance of the data are evaluated. We then derive a statistical range as a reference against which individual METF measurements may be validated. The range is calculated as the two-sided 95% tolerance interval at audiological frequencies. In addition, the mean and 95% confidence interval of the mean are given as references for assessing the validity of a sample group. Finally, we provide a suggested procedure for measuring METFs using the methods described herein.

Strain prediction and benchmark with measurement in the Spallation Neutron Source mercury target without gas injection

The 1.4-MW Spallation Neutron Source (SNS) currently operates as the world's highest time-average power spallation source and uses mercury as the spallation target material. The mercury circulates through a stainless-steel target vessel and heat exchanger loop that removes the heat deposited from the incident proton beam in the target. The mercury vessel is part of the fixed but replaceable target module. The target module is not safety credited in the SNS design, but reliable long life is vital for meeting operational goals and minimizing cost and waste. SNS is a short-pulse ($\ensuremath{\sim}0.7\text{ }\text{ }\ensuremath{\mu}\mathrm{s}$) neutron source with a repetition rate of 60 Hz with 1.0 GeV protons onto the target. The short-pulse operation introduces two mechanisms that threaten the longevity of the mercury vessel. The pulsed target heating is essentially isochoric, which results in a distributed pressure field in the mercury with each pulse. After each pulse, the pressure propagates, interacts with, and strains the stainless-steel vessel. For intermittent times, this pressure field leads to mercury cavitation. The first mechanism of concern for the target lifetime is high-cycle fatigue to the stainless-steel vessel and the second is cavitation erosion. At the onset of the SNS project, the R program sought to address the need for an accurate and practical method to estimate the fatigue life of the mercury vessel. Around 2000, the R team conducted a series of in-beam mercury target experiments at the Weapons Neutron Research Facility at Los Alamos Neutron Science Center. These experiments successfully produced a small database of pulse response strain data. The data were used to develop and benchmark an explicit dynamic finite element analysis technique for estimating target fatigue life. SNS is now a mature facility with about 15 years of operation and 29 SNS target modules consumed. Since 2015, strain measurements have been collected from actual targets, and abundant target vessel strain data are now available in greater detail than was possible in 2000. Variances in pulse response data have been characterized using tolerance interval analysis to benchmark the simulation technique more thoroughly. The simulated results were found to match measurements generally well, but the method is always conservative. A potential adjustment to the cavitation threshold parameter value was suggested. Variances in the pulse response data are moderate, which is largely explained by the fact that data were acquired in 60-Hz burst mode and by the lasting vibration of the vessel between pulses.

Body Weight Distribution and Body Sway in Healthy Female Adults Aged between 51 and 60 Years in Germany—Standard Values

Background: In order to determine possible pathological deviations in body weight distribution and body sway, it is helpful to have reference values for comparison: gender and age are two main influencing factors. For this reason, it was the aim of the present study to present reference values for women between 51 and 60 years of age. Methods: For this study, 101 subjectively healthy female Germans aged between 51 and 60 years (55.16 ± 2.89 years) volunteered and were required to stand in a habitual posture on a pressure measuring platform. Results: The average BMI of this age group was 25.02 ± 4.55 kg/m². The left and right foot showed an almost evenly balanced load distribution with a median load of 52.33% on the left foot [tolerance interval (TR) 38.00%/68.03%; confidence interval (CI) 51.00%/53.33%] and 47.67% on the right foot [TR 31.97%/62.00%; CI 46.67%/49.00%]. The measured median load of the forefoot was 33.33% [TR 21.37%/54.60%; CI 30.67%/36.00%] and that of the rear foot was 66.67% [TR 45.50%/78.63%; CI 64.00%/69.33%]. The median body sway in the frontal plane was 11 mm [TR 5.70 mm/26.30 mm; CI 10.00 mm/11.67 mm] and that of the sagittal plane was 16 mm [TR 7.37 mm/34.32 mm; CI 14.67 mm/18.67 mm]. The median ellipse area was 1.17 cm² [TR 0.29 cm²/4.96 cm²; CI 0.98 cm²/1.35 cm²], the median ellipse width was 0.91 cm [TR 0.42 cm/1.9 cm; CI 0.84 cm/1.02 cm] and its height was 0.40 cm [TR 0.22 cm/0.89 cm; CI 0.38 cm/0.43 cm]. Conclusions: The left-to-right ratio is almost balanced. The load distribution of the forefoot to the rear foot is approximately 1:2. The median body sway values for the frontal and sagittal planes (11 and 16 mm, respectively) agree with other values. The values for the height, body weight and the BMI are comparable to the values of average German women at this age; therefore, the measured values show a presentable cross section of women in the 51–60 age group in Germany. The present data can be used as a basis for women aged 51–60 years and can support the detection of possible dysfunctions as well as injury prevention in the parameters of postural control.

The influence of a possible contamination of the victim's clothing on the estimation of shooting distance in mutual shooting incidents

One of the tools for estimating shooting distance is examination of smokeless powder particle distribution on the target area. Components of the powder that are utilized for this purpose are nitrite anions. The traditional method for detecting nitrite anions mainly involves applying the Griess Test. A known-distance test firing is performed with shootings done at several distances from different targets. The color pattern corresponding to nitrite anions from the crime scene is then compared to the patterns obtained from known distances of the test firing. When a mutual shooting takes place at the crime scene, and a shooter also becomes a shootout victim, it is possible that when examining the shooter as a victim (i.e. target), additional nitrite-containing particles, resulting from his/her shooting, will be present on the shooter-victim clothing. This kind of addition may affect the estimation and practically give a shorter-distance estimation comparing to the actual distance. In this paper, an experimental setup was designed in order to understand if nitrite-containing particles were added to a victim as a consequence of him/her being also a shooter. All of the experiments were predominantly designed to try and minimize the effects of other influencing factors and variables in order to examine if the additions resulting from the firing action affect distance estimation. The experiments involved various types of pistols and distances. The results show that in such a scenario, there are marginal additions of nitrite signals on the victim's shirt. Although the forensic expert's final assessment was within the tolerance interval at all distances, caution should be exercised when attempting to estimate shooting distances in scenarios where the victim also shoots.

A simple and green liquid chromatography method for the determination of ibuprofen in milk-containing simulated gastrointestinal media for monitoring the dissolution studies of three-dimensional-printed formulations.

A fast and green ultra-high-performance liquid chromatographic method was developed for the determination of ibuprofen in milk-containing simulated gastrointestinal media to monitor the dissolution of three-dimensional printed formulations. To remove interfering compounds, protein precipitation using methanol as a precipitation reagent was performed. The separation of the target analyte was performed on a C18 column using a mobile phase consisting of 0.05% v/v aqueous phosphoric acid solution: methanol, 25:75% v/v. Method validation was conducted using the total error concept. The β-expectation tolerance intervals did not exceed the acceptance criteria of±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between ─1.1 and +3.2% for all analytes, while the relative standard deviation values for repeatability and intermediate precision were less than 2.8% and 3.9%, respectively. The achieved limit of detection was 0.01μg/ml and the lower limit of quantitation was established as 2μg/ml. The proposed method was simple, and it required reduced organic solvent consumption following the requirements of Green Analytical Chemistry. The method was successfully employed for the determination of ibuprofen in real biorelevant media obtained from dissolution studies.

Evaluation of Fluid Overload by Bioelectrical Impedance Vectorial Analysis

Early detection and management of fluid overload are critically important in acute illness, as the impact of therapeutic intervention can result in decreased or increased mortality rates. Accurate fluid status assessment entails appropriate therapy. Unfortunately, as the gold standard method of radioisotopic fluid measurement is costly, time-consuming, and lacks sensitivity in the acute care clinical setting, other less-accurate methods are typically used, such as clinical examination or 24 h output. Bioelectrical impedance vectorial analysis (BIVA) is an alternative impedance-based approach, where the raw parameter resistance and reactance of a subject are plotted to produce a vector, the position of which can be evaluated relative to tolerance intervals in an R-Xc graph. The fluid status is then interpreted as normal or abnormal, based on the distance from the mean vector derived from a healthy reference population. The objective of the present study is to demonstrate how to evaluate the presence of fluid overload through bioelectrical impedance vectorial analysis and the impedance ratio measured with tetrapolar multi-frequency equipment in patients admitted to the emergency department.

Green homogeneous liquid-liquid microextraction at high salinity conditions for the determination of nimesulide in human urine with the aid of experimental design

Green homogeneous liquid-liquid microextraction (HLLME) under high salinity conditions was proposed for the determination of nimesulide in human urine. The proposed analytical scheme consisted of the mixing of the appropriate volume of acetonitrile and sample followed by the addition of Na2SO4 solution to obtain phase separation. Following the extraction of the drug from the urine samples, high-performance chromatography-diode array detection (HPLC-PDA) was used for its determination. The main factors influencing the performance of the HLLME method were studied and optimized using a two-step experimental design (Plackett-Burman, Central Composite Design). The HLLME-HPLC-PDA method was systematically validated using the accuracy profiles. The detection limit was adequate and estimated to be 0.03 μg mL−1. The mean analytical bias (expressed as relative error) ranged between ─ 2.9–3.6% and the relative standard deviation (RSD) was better than 3.7%. Moreover, the β-expectation tolerance intervals were in the range of ±15% demonstrating that 95% of the results will fall within the defined bias limits. The ruggedness of the herein developed protocol was assessed using Monte-Carlo simulations followed by capability analysis. The proposed scheme was applied for the determination of the drug in real urine samples following the administration of pharmaceutical formulations that contained nimesulide.

Temperature-dependent tissue residue depletion and withdrawal time of orally administered tylosin tartrate in starry flounder, Platichthys stellatus

The purpose of this study was to demonstrate the effect of water temperature on residue depletion and withdrawal times (WTs) of tylosin in serum, muscle plus skin, liver, and kidney of the starry flounder, Platichthys stellatus, post oral (PO) administration of tylosin tartrate (TT) at 10 mg/kg dosage for 5 consecutive days. Samples were taken 3, 5, 7, 14, and 21 days post last dose, and tylosin was quantified using liquid chromatography-tandem mass spectrometer (HPLC-MS/MS). The elimination half-life (T1/2) for each tissue was calculated using ln2/k and the WT was calculated using the WT 1.4 software at 99% statistical tolerance limit with 95% confidence. High concentrations of tylosin were detected in liver and kidney samples. A decrease in water temperature from 22 to 13 °C prolonged the T1/2 in all the tissue samples. The T1/2 were 1.82 and 6.19 d in serum, 2.63 and 3.92 d in muscle plus skin, 4.53 and 13.59 d in liver, and 10.83 and 28.88 d in kidney at 22 and 13 °C, respectively. The WTs for tylosin in the kidney, liver, muscle plus skin, and serum samples were in the following order: 111.7 d > 50.7 d > 20.1 d > 0 d at 22 °C and > 120 d > 81.3 d > 27.9 d > 0 d at 13 °C, respectively. Furthermore, WT (with T1/2) and water temperature were negatively correlated, in all the tissue samples. Further, our results suggest a WT of 28 d for TT (marker residue; tylosin A) in the muscle plus skin tissue (target tissue) of P. stellatus for its safe consumption. Overall, our study provides a theoretical basis for the effect of water temperature on the drug residue pattern and elimination kinetics of PO administered TT in P. stellatus, which is important for improving food safety in farmed fish.

Fast acquisition of left and right ventricular function parameters applying cardiovascular magnetic resonance in clinical routine – validation of a 2-shot compressed sensing cine sequence

Objectives. To evaluate if cine sequences accelerated by compressed sensing (CS) are feasible in clinical routine and yield equivalent cardiac morphology in less time. Design. We evaluated 155 consecutive patients with various cardiac diseases scanned during our clinical routine. LV and RV short axis (SAX) cine images were acquired by conventional and prototype 2-shot CS sequences on a 1.5 T CMR. The 2-shot prototype captures the entire heart over a period of 3 beats making the acquisition potentially even faster. Both scans were performed with identical slice parameters and positions. We compared LV and RV morphology with Bland-Altmann plots and weighted the results in relation to pre-defined tolerance intervals. Subjective and objective image quality was evaluated using a 4-point score and adapted standardized criteria. Scan times were evaluated for each sequence. Results. In total, no acquisitions were lost due to non-diagnostic image quality in the subjective image score. Objective image quality analysis showed no statistically significant differences. The scan time of the CS cines was significantly shorter (p < .001) with mean scan times of 178 ± 36 s compared to 313 ± 65 s for the conventional cine. All cardiac function parameters showed excellent correlation (r 0.978–0.996). Both sequences were considered equivalent for the assessment of LV and RV morphology. Conclusions. The 2-shot CS SAX cines can be used in clinical routine to acquire cardiac morphology in less time compared to the conventional method, with no total loss of acquisitions due to nondiagnostic quality. Trial registration ISRCTN12344380. Registered 20 November 2020, retrospectively registered.

Economic optimization of acceptance interval in conformity assessment: 1. Process with no systematic effect

In inspections for conformity assessment, an acceptance interval smaller than the tolerance interval is often determined in order to reduce the risk of consumers obtaining non-conforming items in the market. The presence of non-conforming items in the market impairs the evaluation of items by customers and may have an impact on revenue by decreasing prices. However, setting too small an acceptance interval reduces the revenue from the process by decreasing the number of the items available in the market. We thus propose a method to determine the optimum acceptance interval in conformity assessment by means of maximization of the revenue from processes. For this purpose, we give a mathematical model for the price of an item and its cost in the production process. Through theoretical analysis and simulations, it is shown that a parameter in the price model is the key in the optimization. In this paper we report a method for processes where no systematic effect component of measurement uncertainty exists, and in part 2 of this series we will report an extended method in which systematic effects are taken into consideration.

New method to optimize no-load noise of power transformers based on core design &amp; transformer operating conditions

This paper introduces a new algorithm to calculate and optimize no-load noise (sound pressure) of power transformers, and to identify iron sheet parameters. The calculation consists of two steps: the 1st step consists in calculating an initial sound pressure level (A-Evaluation) which has approx. 70 % accuracy within a tolerance interval of ±2dB (A). The 2nd step consists in estimating the expected deviation from the initial calculation to reach 90 % accuracy in the final results. This deviation could be due to material handling, quality tolerance, core manufacturing, etc. The optimization process consists of two parts: the 1st part takes place before choosing a certain iron sheet for calculation to identify the sheet parameters required for computational accuracy (“Sheet Optimization”). The 2nd part consists in considering a core design with an undesirable sound pressure level in order to reduce it to an acceptable limit. This part takes into account the other limitations such as no-load losses and transformer dimensions (“Design Optimization”). For new iron sheets in the market, there is no measurement history to rely on. However, the algorithm is also capable of identifying the sheet parameters for calculation based on the available algorithm data base and the magnetostriction measurements of the iron sheet manufacturer.

Salt-Induced Homogeneous Liquid–Liquid Microextraction of Piroxicam and Meloxicam from Human Urine Prior to Their Determination by HPLC-DAD

A salt-induced homogeneous liquid–liquid microextraction (SI-HLLME) protocol combined with high-performance liquid chromatography–diode array detection is presented for the first time for the determination of piroxicam and meloxicam in human urine. The main parameters affecting the performance of the sample preparation protocol were optimized by means of a two-step experimental design (i.e., 2-level fractional factorial design and Box–Behnken design). Following its optimization, the proposed method was thoroughly validated in terms of the total error concept in order to take into consideration the random and systematic errors. For the target analytes, accuracy profiles were constructed, and they were used as graphical decision-making tools. In all cases, the β-expectation tolerance intervals complied with the acceptance criteria of ±15%, proving that 95% of future results will fall within the defined bias limits. The limits of detection were 0.02 μg mL−1 and 0.03 μg mL−1 for piroxicam and meloxicam, respectively. The relative standard deviations were lower than 4.4% in all cases, and the mean relative biases ranged between −5.7 and 3.4% for both drugs. The proposed scheme is simple and rapid, while it is characterized by high sample throughput. Moreover, SI-HLLME requires reduced sample and reagent consumption, according to the requirements of Green Analytical Chemistry.

Manual 3D Control of an Assistive Robotic Manipulator Using Alpha Rhythms and an Auditory Menu: A Proof-of-Concept

Brain–Computer Interfaces (BCIs) have been regarded as potential tools for individuals with severe motor disabilities, such as those with amyotrophic lateral sclerosis, that render interfaces that rely on movement unusable. This study aims to develop a dependent BCI system for manual end-point control of a robotic arm. A proof-of-concept system was devised using parieto-occipital alpha wave modulation and a cyclic menu with auditory cues. Users choose a movement to be executed and asynchronously stop said action when necessary. Tolerance intervals allowed users to cancel or confirm actions. Eight able-bodied subjects used the system to perform a pick-and-place task. To investigate the potential learning effects, the experiment was conducted twice over the course of two consecutive days. Subjects obtained satisfactory completion rates (84.0 ± 15.0% and 74.4 ± 34.5% for the first and second day, respectively) and high path efficiency (88.9 ± 11.7% and 92.2 ± 9.6%). Subjects took on average 439.7 ± 203.3 s to complete each task, but the robot was only in motion 10% of the time. There was no significant difference in performance between both days. The developed control scheme provided users with intuitive control, but a considerable amount of time is spent waiting for the right target (auditory cue). Implementing other brain signals may increase its speed.

Development and Validation of an HPLC-UV Method for the Dissolution Studies of 3D-Printed Paracetamol Formulations in Milk-Containing Simulated Gastrointestinal Media.

Herein, a simple and rapid HPLC method for the determination of paracetamol milk-containing biorelevant media is proposed. The separation of the analyte from the milk-containing biorelevant media was accomplished isocratically using a mobile phase containing 25 mM phosphate buffer (pH = 3.0) and methanol, 80:20, v/v at a flow rate of 1 mL min−1. Following a protein precipitation-based sample clean-up, a thorough investigation of the effect of the precipitation reagent (methanol, acetonitrile, 10% v/v trifluoroacetic acid solution) on the analyte recovery was performed. The matrix effect was assessed in each biorelevant medium by comparing the slopes of the calibration curves of aqueous and matrix-matched calibration curves. The method was comprehensively validated using the accuracy profiles. The β-expectation tolerance intervals did not exceed the acceptance criteria of ±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between −4.5 and +3.9% for all analytes, while the RSD values for repeatability and intermediate precision were less than 2.7% and 3.0%, respectively. The achieved limit of detection (LOD) was 0.02 μg mL−1 and the lower limits of quantitation (LLOQ) were established as 10 μg mL−1, which corresponded to 2% of the highest expected concentration of paracetamol. The proposed scheme was utilized for the determination of paracetamol in dissolution studies of its 3D-printed formulation in milk-containing biorelevant media.

HPLC Determination of Colistin in Human Urine Using Alkaline Mobile Phase Combined with Post-Column Derivatization: Validation Using Accuracy Profiles.

In this study, the development, validation, and application of a new liquid chromatography post-column derivatization method for the determination of Colistin in human urine samples is demonstrated. Separation of Colistin was performed using a core–shell C18 analytical column in an alkaline medium in order (i) to be compatible with the o-phthalaldehyde-based post-column derivatization reaction and (ii) to obtain better retention of the analyte. The Colistin derivative was detected spectrofluorometrically (λext/λem = 340/460 nm) after post-column derivatization with o-phthalaldehyde and N-acetyl cysteine. The post-column derivatization parameters were optimized using the Box–Behnken experimental design, and the method was validated using the total error concept. The β-expectation tolerance intervals did not exceed the acceptance criteria of ±15%, meaning that 95% of future results would be included in the defined bias limits. The limit of detection of the method was adequate corresponding to 100 nmol·L−1. The mean analytical bias (expressed as relative error) in the spiking levels was suitable, being in the range of −2.8 to +2.5% for both compounds with the percentage relative standard deviation lower than 3.4% in all cases. The proposed analytical method was satisfactorily applied to the analysis of the drug in human urine samples.

Assessing individual equivalence in parallel group and crossover designs: Exact test and sample size procedures.

The consideration of individual equivalence provides an essential alternative to average equivalence in two-group comparative studies. A common procedure for declaring individual equivalence adopts the tolerance intervals of the designated proportions of measurement differences. This statistical practice is a direct generalization of the widely used two one-sided tests (TOST) for average equivalence. Such TOST extensions often do not have adequate control of Type I error and result in excessively conservative tests. To signify and resolve the underlying issues of existing methods, this paper presents exact tests for assessing individual equivalence between two treatments under parallel group and crossover designs. Rigorous evaluations are conducted to clarify the discrepancy of critical values and Type I error probabilities between the equivalence procedures. The findings elucidate the shortcoming of the TOST technique and the advantage of the proposed approach. The associated power and sample size calculations are also justified through simulation studies.

Analytical Uncertainty in Animal Feed Laboratories: A Current Evaluation of AAFCO Proficiency Testing Data for Select Analytes

The animal feed regulatory community utilizes analytical variations (AVs) that account for the normal variability that occurs within and between laboratories. The AV was created using the Association of American Feed Control Officials (AAFCO) proficiency testing (PT) program results and represent the coefficient of variation times 2 (2 CV). This study was performed to assess the accuracy of the published AVs within the association’s Official Publication (OP) using AAFCO PT data from 2014 to 2020. This study also reevaluated the current AV values by applying the concept of the measurement uncertainties including the expanded uncertainty (U), Horwitz value, and 2 CV for the assessment of the label guarantees. Although greater variations were observed at lower concentrations, the majority of data points from the PT rounds showed an acceptable reproducibility for the select analytical methods except for cobalt, fat, fiber, moisture, and selenium where 2 CV was higher than the current AAFCO AV. Regression models were developed based on the 95% tolerance interval of expanded uncertainty and 2 CV and were validated using the 2019-2020 AAFCO PT data. The validation data fell within the expanded uncertainty and 2 CV model bounds indicating the new models were fit-for-purpose and accurately characterized current AAFCO PT data. The study results imply the AAFCO AV and its issues need to be better understood to improve an accuracy and traceability of the laboratory’s measurement and thus regulatory decisions to help animal feed producers and processors lower economic losses.

In situ synthesis of monolithic sol–gel polyethylene glycol-based sorbent encapsulated in porous polypropylene microextraction capsules and its application for selective extraction of antifungal and anthelmintic drugs from human urine

Herein, a monolithic sol–gel polyethylene glycol-based sorbent (PEG) has been in situ synthesized within two conjoined porous polypropylene microextraction capsules and subsequently applied for the microextraction of triazoles and benzimidazoles drugs from human urine. A cylindrical bar magnet was incorporated into the device, offering the ability of spinning when it is placed in a magnetic field resulting in a stand-alone “all-in-one” extraction device. Among other sorbent tested, the sol–gel PEG 300 coated microextraction capsules were found to be beneficial for the extraction of the target analytes. The analysis of the drugs was performed using high-performance liquid chromatography and photodiode array detection (HPLC-PDA). Detailed investigation of the main parameters that affect the extraction performance (i.e., dimensions of the microextraction capsules, sample volume, extraction time, ionic strength, stirring rate, elution time, type of eluent, volume of eluent) was conducted to find the optimum conditions for the extraction procedure. The method was thoroughly validated using the total-error concept. The β-expectation tolerance intervals did not exceed the acceptance criteria of ± 15% meaning that 95% of future results will be included in the defined bias limits. The lower limits of quantitation (LLOQs) of the method were adequate, corresponding to 0.1 and 0.25 μg mL−1 for triazoles and benzimidazoles, respectively. The mean analytical bias in the spiking levels was satisfactory, ranging between ─ 3.8 to + 6.7 % while the relative standard deviation (RSD) was lower than 5.6 %. Finally, the sol–gel PEG 300 encapsulated microextraction capsules were found to be reusable for at least 15 extraction cycles. The developed approach was successfully applied in the analysis of the selected drugs in urine samples.

Isogeometric interval size optimization of beam structures

Based on beam theory in the framework of isogeometric analysis, an interval size optimization for beam structures is proposed, which not only realizes the lightweight of the beam structure, but also ensures the reliability of the structure. The exact geometry of the beam structure is expressed by non-uniform rational B-splines. According to Timoshenko beam theory, the isogeometric beam stiffness matrix is calculated, and static analysis is carried out. Using Taylor’s formulation and interval extension of the function, the manufacturing tolerance interval optimization model of the beam structure is transformed into a deterministic optimization model. The section size and tolerance of the beam structure are taken as design variables, the mass is taken as the objective function, and the torsional stiffness and bending stiffness are taken as constraint functions. The calculation formulation of second-order sensitivity is deduced, and the optimized results of the beam structure are obtained by using the method of moving asymptotes. The effectiveness of the optimization strategy of this method is proven by three numerical examples. This paper provides isogeometric analysis method to realize the section interval optimization of beam structures without meshing, which guides the lightweight design of beam structures.

Voltammetric determination of pilocarpine hydrochloride in ophthalmic solutions

An express method for the determination of pilocarpine hydrochloride (PHC) in ophthalmic solutions based on titration of the analyte with photogenerated iodine obtained by irradiation of potassium iodide in the presence of a mixture of sensitizers (sodium eosinate:fluorescein:auramine in a molar ratio of 1:1:1) at pH 5.6 has been developed. The titrant content in the cell was controlled by the voltammetric method (amperometric titration with two polarized electrodes): during the PHC titration a decrease in the current strength in the circuit of the amperometric installation was observed. Stabilization of the current in the circuit of the amperometric installation indicated the completeness of the reaction, and, thus provided the possibility of estimation of the PHC content in a dosage form. The measured generation time required to replenish the loss of titrant upon further irradiation of the solution was also used to calculate the PHC content in the preparation. Testing of the developed technique was carried out on an ophthalmic drug «Pilocarpine, eye drops 1%». Introduction of more than 20.0 g of boric acid used as a preservative agent into the cell resulted in a slight underestimation of the PHC content. The determined PHC content in the sample of series 60918 is 0.93 – 0.94% (measured by generation time) is lower than the tolerance interval set by order of the Ministry of Health of the Russian Federation No. 751n, October 26, 2015 (0.95 – 1.05%). The PHC content in other samples falls within the recommended range, which indicates that the drug quality complies with GMP standards. A linear dependence of the analytical signal on the PHC concentration is observed in the range of 15 – 500 μg. The calculated detection and quantitation limits are 5.6 and 18.6 μg, respectively. The developed photochemical method for PHC determination in the drug «Pilocarpine, eye drops 1%» meets the requirements set forth in the manual for the validation of bioanalytical methods. The method is easy to use and does not require expensive equipment.