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High-concentration and low-viscosity antibody formulations are necessary when administering these solutions subcutaneously (SC) due to limitations on injection volume. Here we show a method to decrease the viscosity of monoclonal antibody solution by protein–polyelectrolyte complex (PPC) with poly- l -glutamic acid (polyE). The viscosity of omalizumab solutions was 90 cP at the concentration of 150 mg/mL. In the presence of 20–50 mM polyE, the viscosity of PPC solution of 150 mg/mL omalizumab dramatically decreased below 10 cP due to the formation of crowded solution. The crowded state of PPC, named aggregated PPC (A-PPC), contained water droplets with a diameter of 10 μm or larger with low antibody concentrations. In the presence of 60 mM or more polyE, the omalizumab solution was transparent with the viscosity of 40 cP or less, named soluble PPC (S-PPC). More importantly, the solutions of both A-PPC and S-PPC were fully redissolved by the addition of phosphate saline buffer confirmed by secondary structure, the amount of aggregates, and binding activity to antigen.

The current analytical exploration illustrated developing a reversed-phase high-performance liquid chromatography (RP-HPLC) technique and consequent substantiation for analyzing lamotrigine (LAM) active pharmaceutical ingredient (API) using a Quality-by-design (QbD) approach (Central Composite Design), in bulk product as well as in the tablet formulations. In this experiment, based on systematic scouting, four key components (viz., mobile phase, column, flow-rate, and wavelength) were studied by the RP-HPLC method. 13 experimental runs were done with acetonitrile (ACN) (40-60% v/v) having flow-rate in the range 0.8 mL/min to 1.2 mL/min. The proposed analytical method was thoroughly corroborated in terms of ruggedness linearity, robustness, accuracy, and precision in accordance with ICH guideline Q2A and ICH guideline Q2B. Under the optimum chromatographic environment; Intersil C8 column of 250 mm length, 4.6 mm (i.d.); 20 μL injection volume; and mobile phase ACN: Methanol (60:40 v/v), a retention time of 2.542 min was noticed at 220 nm detection wavelength. The method was found to be extremely reproducible, accurate, linear, precise, robust, and economically adequate to execute the estimation. The intended analytical technique was thoroughly assessed through statistical tools and could be an imperative concern for the habitual scrutiny of LAM in bulk products and its formulation.

A tight conglomerate reservoir is a kind of unconventional reservoir with strong heterogeneity, and CO2 injection is an economical and environmentally friendly method to enhance tight oil recovery. Supercritical CO2 is a very promising fluid medium for unconventional reservoir development due to its gas-liquid dual properties. In this study, the production effects of supercritical CO2 and non-supercritical CO2 in tight conglomerate reservoirs were quantitatively analyzed by huff and puff simulation experiments conducted under reservoir conditions (formation pressure 37 MPa, temperature 89 °C). Also, the influencing factors of CO2 huff and puff production, including injection volume, soaking time, and throughput cycles, were investigated. The results showed that supercritical CO2 improves the recovery by 4.02% compared with non-supercritical CO2. It could be seen that supercritical CO2 plays a positive role in improving tight conglomerate reservoirs. The optimal injection volume, soaking time, and throughput cycles were determined to be 0.50 PV, 2 h, and 3 cycles, respectively. This paper provides an important basis for the study of supercritical CO2 production in tight conglomerate reservoirs.

Aim: To develop new selective and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) approach for the quantification of antifungal drug Luliconazole integrate with corticosteroid drug Clobetasol Propionate in a synthetic mixture. Methods: The method was validated to achieve International Conference Harmonization (ICH) requirements. Chromatographic separation was carried out by isocratic technique on a reversed-phase Inertsil C18 column (5 µm, 250mm x 4.6mm i.d with the mixture of Acetonitrile: Water pH adjusted with H3PO4 (60: 40) and UV detection at 264 nm. The compounds were eluted at a flow rate of 1.0 mL/min with an injection volume of 20μL. Results: The calibration curves were linear (r2 > 0.999) over the concentration range 10-200 μg/mLfor Luliconazole and 5-100 μg/mL for Clobetasol Propionate. The average retention times for Luliconazole and Clobetasol Propionate were 3.16 and 6.94 min, respectively. The % RSD for the proposed method was found to be less than %2. The % recovery was found to between 99.22-99.48% for the developed method. Conclusion: The developed method is simple, rapid, precise, and accurate and hence was successfully applied for the determination of Luliconazole and Clobetasol Propionate in a synthetic mixture.

With the increased presence of novel psychoactive substances (NPSs) in casework, drug analysis has become more challenging. To address these challenges, new screening technologies with improved specificity are being implemented, allowing for the creation and adoption of targeted confirmatory analyses that produce more conclusive results. This paper outlines a six-step, data-driven, framework to develop and evaluate gas chromatography mass spectrometry (GC-MS) methods for targeted classes of drugs. The process emphasizes maximizing retention time differences (to minimize the potential for retention time acceptance windows to overlap) and understanding the tradeoffs between sensitivity and reproducibility using a test solution containing pairs of compounds that are difficult to distinguish. The method is then evaluated by expanding the panel of compounds analyzed, identifying limitations in compound discrimination, comparing to current methods, and analyzing representative casework to establish usability. To demonstrate this framework, a method for synthetic cannabinoids was created. The developed method utilizes a DB-200 column and an isothermal temperature program. It was found that sensitivity could be adjusted, without compromising reproducibility, by altering the split ratio and injection volume. The targeted method successfully differentiated 50 cannabinoids based on either retention time differences or mass spectral dissimilarity – determined using a newly developed spectral comparison test. Compared to the general method investigated for comparison, the targeted method was an order of magnitude more sensitive and a minute shorter while providing major increases in retention time differences. This framework can be implemented and adapted to develop targeted methods for other applications or compound classes.

The aim of this study is to validate a new HPLC-FIA method for routine analytical control of cyclosporine injectable preparations and to evaluate the routine analytical control with this technic.Cyclosporine dosage was carried out by the HPLC-FIA method. The column was replaced by a PEEK (polyetheretherketone) loop tubing. The mobile phase consisted of ultrapure water. The injection volume was 1μL with a flow rate of 1mL/min. All determinations were performed at 35°C. The detection was carried out at 210nm. The accuracy profile method was used to validate the HPLC-FIA assay of cyclosporine. Routine control was applied for each cyclosporine preparation using the HPLC-FIA developed method. An acceptance limit of ±10% of the theoretical concentration has been set for the conformity of the preparation.The accuracy profile shows the validity of our method for the dosage of cyclosporine in the concentration range studied (0.5-2.5mg/mL) with good linearity (correlation coefficient0.999), high precision (the relative standard deviation [RSD] values, for both repeatability and intermediate precision, were3%) and acceptable trueness (the relative biases were found2%). In our study, 220 injectable cyclosporine preparations were analyzed: 85% were compliant. All analyzes were conform after a second standardized homogenization of 10 shakes.The proposed HPLC-FIA method is a reliable, fast, simple, precise method that can be easily used for the routine quality control of cyclosporine injectable preparations.

Background During diagnostic cerebral angiography, the contrast bolus injected into a vessel can cause substantial changes in baseline pressures and flows. One potential, and serious complication is the re-rupture of aneurysms due to these injections. The goals of this in vitro study were to evaluate the effect of injection conditions on intraneurysmal pressure changes during angiography. Methods A silicone replica of a complete circle of Willis model with ophthalmic, anterior communicating, and basilar tip aneurysms was connected to a physiologically accurate flow pump. Contrast injections were performed under different conditions (carotid or vertebral vessel imaging, catheter diameter, injection rate, injection time, and arterial blood flow rate) and the pressure in each aneurysm was recorded before and during each injection. The effect of injection conditions on percentage increase in aneurysm pressures was statistically assessed. Additionally, the effect of the distance between the aneurysm and the catheter-tip on aneurysmal pressures was assessed. Results Mean intraneurysmal pressures during injection (84.5 ± 10.8 mmHg) were significantly higher than pre-injection pressures (80.4 ± 10.6 mmHg, p Conclusions Increasing contrast injection rates and decreasing catheter diameters are correlated to intraneurysmal pressure increases during angiography irrespective of the distance to the catheter tip. Future in vivo studies are required to confirm these findings and determine whether the amplitude of pressure increases with commonly used injection rates can be clinically detrimental.

Excessive water production is one of the biggest problems commonly found in the brown water-flood field. There are two treatments of water shut-off (WSO) in hydrocarbon wells. The mechanical WSO is a routine operation that is commonly carried out and is part of standard well work; meanwhile, the chemical WSO is a specific treatment. The study aims to identify the effect of polymer concentration, injection rate, and soaking time on the effectiveness of chemical WSO with cross-linked polymers in a specific field. The study proposes and analyses the optimization of this treatment in the 7E Sandstone field by utilizing a conceptual simulation model. Geographically, this field is located in the Central Sumatera basin. The field is a moderately homogenous sandstone. Last decade, the 7E field was associated with excessive water production issue, some mechanical WSO has been done to solve the problem, but less effective and inefficient. Hence chemical WSO job comes as a promising option to overcome this problem robustly. The cross-link polymer injection treatment is the action of blocking water from entering and reaching production wells by using a mixture of polymer, cross-linker, and water. A base case of the conceptual model has been developed, then over twenty injection scenarios wide-ranging based on polymer concentrations are implemented in the model. Each of these concentration schemes is simulated using different injection flow rates for the total injection volume of 2000 bbl. The injection rate sets at 1000 bbl/day for twice injection and 2000 bbl/day for one injection. Soaking time is settled for one, two, and three days to give time for generating gelatin. A comparison of water production before and after the WSO is used to investigate WSO effectivity. The simulation result mentions that the WSO implementation can decrease excess water from 385,143 bbl to 186,189 bbl.

Subcutaneous (SC) delivery of biologics has traditionally been limited to fluid volumes of 1–2 mL, with recent increases to volumes of about 3 mL. This injection volume limitation poses challenges for high-dose biologics, as these formulations may also require increased solution concentration in many cases, resulting in high viscosities which can affect the stability, manufacturability, and delivery/administration of therapeutic drugs. Currently, there are technologies that can help to overcome these challenges and facilitate the delivery of larger amounts of drug through the SC route. This can be achieved either by enabling biologic molecules to be formulated or delivered as high-concentration injectables (>100 mg/mL for antibodies) or through facilitating the delivery of larger volumes of fluid (>3 mL). The SC Drug Delivery and Development Consortium, which was established in 2018, aims to identify and address critical gaps and issues in the SC delivery of high-dose/volume products to help expand this delivery landscape. Identified as a high priority out of the Consortium’s eight problem statements, it highlights the need to shift perceptions of the capabilities of technologies that enable the SC delivery of large-volume (>3 mL) and/or high-dose biologics. The Consortium emphasizes a patient-focused approach towards the adoption of SC delivery of large-volume/high-concentration dosing products to facilitate the continued expansion of the capabilities of novel SC technologies. To raise awareness of the critical issues and gaps in high-dose/volume SC drug development, this review article provides a generalized overview of currently available and emerging technologies and devices that could facilitate SC delivery of high-dose/volume drug formulations. In addition, it discusses the challenges, gaps, and future outlook in high-dose/volume SC delivery as well as potential solutions to exploit the full value of the SC route of administration.

The analytical method was developed and validated for determination of acyclovir in Tablet by High performance liquid chromatography. The separation was carried out on Luna C18 column (150*4.6mm, 5μm). The mobile phase consists of methanol: water in the ratio 50:50 at flow rate 1ml/min with diode array detector wavelength at 248 nm. The column temperature was adjusted at 38° ± 0.8±C with injection volume 20μl. The retention time of acyclovir was 2.718min. The linearity of the calibration curve was linear over the concentration range 40-60μg/ml (r2=1). The validation was carried out as per ICH guidelines. The development method was easy, rapid, linear, precise, accurate and consistent.

An experimental technique is developed to investigate the dynamic imbibition displacement mechanism in tight sandstone formations of the Yanchang group of the Ordos basin. By combining the dynamic imbibition core flooding experiments and NMR technique, the effects of the injection volume and rate on displacement efficiency are investigated. Moreover, the displacement efficiency of dynamic imbibition is compared with that of static imbibition. This study gains insights into the micromechanisms of dynamic imbibition in tight sandstone formations. It is found that the relative displacement efficiency of dynamic imbibition increases with the increase of injection volume. But the increment amplitude decreases with the increase of injection volume. With the same injection volume, the core displacement efficiency of dynamic imbibition with high permeability is obviously improved. However, the core displacement efficiency decreases rapidly with the increase of injection volume. Optimal injection volumes are recommended for tight sandstone formations with different permeabilities. With the increase of the displacement rate, the core displacement efficiency of dynamic imbibition shows a trend of first rising and then declining. There exists an optimal displacement rate in dynamic imbibition displacement, and the optimal displacement rate almost linearly increases with the increase of core permeability. The static imbibition displacement efficiency increases with the increase of soaking time, but the increment amplitude slows down obviously. The displacement efficiency of static imbibition in small pores is higher than that of dynamic imbibition. The displacement efficiency of dynamic imbibition in large pores or microcracks is significantly higher than that of static imbibition. This study provides theoretical support for the optimization and improvement of the waterflooding recovery process in tight sandstone reservoirs.

2-(4-Chlorophenyl)succinic acid was successfully enantioseparated by countercurrent chromatography using hydroxypropyl-β-cyclodextrin as chiral selector. A two-phase solvent system composed of n-hexane-ethyl acetate-0.1 mol/L phosphate buffer with pH 2.65 (5:5:10, v/v) was selected. Enantioselective liquid-liquid extraction was used to optimize the enantioseparation conditions. Meanwhile, the influence of injection volume on resolution in countercurrent chromatography was investigated and a linear relationship between the inflection point of injection volume and sample loading was tentatively obtained. The peak resolution will decrease significantly when the injection volume over the inflection point was used. In addition, it could be found that the smaller amount of sample loading, the larger impact of injection volume on resolution could be observed, which might serve as a good reference for the selection of sample volume in enantioseparations by countercurrent chromatography. Under optimized conditions, 20 mg of 2-(4-chlorophenyl)succinic acid racemate dissolved in 10 mL of aqueous phase was successfully enantioseparated by countercurrent chromatography. The recovery for both of the enantiomer of (±)-2-(4-chlorophenyl)succinic acid reached within 70-75% with a purity of 99.0%.

Hydrogen-peroxide-based low-temperature sterilization is a new sterilization technology for temperature-dependent medical devices. The effect of the process parameters of hydrogen-peroxide-based sterilizer on the sterilization performance of process challenge devices (PCDs) needs to be investigated. Sterilant amount, operating temperature, vacuum pressure, diffusion time, and chamber loading of the sterilizer on the sterilization performance of PCDs were adjusted. Seven PCDs with various morphologies and material containing biological indicators (BI) (EZTest, Geobacillus stearothermophilus) were used to evaluate the sterilization performance. The sterilization success rates of PCDs were 86, 71, and 57% with controlled temperature and pressure, diffusion time, and sterilant volume injection, respectively. The PCD material and structure also obviously affected sterilization performance. The sterilization of PCD A is the least successful for all parameters. Meanwhile, the sterilization of PCD B was influenced by the diffusion time and the sterilant injection volume. PCD B and PCD C were successfully sterilized by controlling the temperature and pressure. The weights and volume of the sterilization loading chamber resulted in a different sterilization performance. Sterilization performances of PCD 1, PCD 2, and PCD 3 were

Fast, simple, accurate, and reproducible reverse phase-high-performance liquid chromatography method with direct ultraviolet measurement of memantine hydrochloride in tablets was developed, without any chemical derivatization pretreatment. Three main problems appear during chromatographic analysis of memantine: detection, achieving appropriate column retention, and limited choice of mobile phase components, as a result of memantine molecular structure. Among more than 35 tested columns, the best retention and peak symmetry yielded two C8 and three C18 columns with different characteristics, at a temperature of 30°C, mobile phase composed of 1%, v/v, acetonitrile and 99%, v/v, of 0.05-0.1% phosphoric acid or 2.5-5 mmol phosphate buffer, at flow rate of 1 mL/min and injection volume of 5 µL. The retention time of memantine was between 2.6 and 4 min. Both mobile phase concepts showed perfect linearity, precision, and accuracy. This is the first successful and reproducible direct reverse phase-high-performance liquid chromatography-ultraviolet quantification method for memantine.

Capillary electrophoresis (CE) is a high-efficiency method for aptamer selection, which exhibits many merits of high resolution, rapid separation, little sample consumption, and no immobilization. However, the influence of injection input on CE systematic evolution of ligands via exponential enrichment (SELEX) is controversial because the low injection volume may result in an insufficient capacity of the oligonucleotides library. In this research, neuron-specific enolase (NSE) was used as a model protein to investigate the effects of library input capacity on aptamer selection for clarifying the validity of CE-SELEX. Four different concentrations of initial libraries (0.1, 1, 10 and 100 μmol/L) were utilized into aptamer selection. The affinity of the initial library and sub-libraries after three rounds of selection were evaluated. The results showed that there was no significant difference in the affinity of four different sub-libraries, and aptamers with micromolar dissociation constant (KD) were all obtained after two rounds of selection. In addition, the sequences obtained via high concentration ssDNA library screening were more diverse, but the affinity of them was not enhanced. The NSE aptamer Seq qN-01 obtained by two rounds of selection had a KD of (4.72 ± 0.15) μmol/L, and also presented a good specificity. In conclusion, library input capacity could increase the sequence diversity but had no considerable effects on the efficiency of aptamer selection.

Hypodermic needles and syringes are currently the main route of the transdermal administration. Many complaints associated with needle-stick injuries, needle phobia, and needle abuse have motivated the development of alternative drug delivery strategies. Pneumatic needle-free injections stand out from various alternative strategies because of the convenience in adjusting the driving pressure and the injection volume. This study proposed a novel control method of the pneumatic needle-free injection for delivering larger volume drugs to the target sites at desired rates and time by controlling the driving pressure. The dynamic characteristics of this injection mode were evaluated in the impact experiments and the results confirmed the reliability of this controllable system in controlling the outlet pressure and jet velocity. The injection performances of it were compared with that of other injection modes through in vivo and in vitro experiments. This controllable system was able to control the injection depth and it was more conducive to the lateral diffusion of the liquid jets in gelatin. Moreover, it could not only enlarge the diffusion of diclofenac solution in rats, but also accelerate the metabolism of diclofenac solution in rats. All experimental results confirmed the reliability of this controllable injection system.

Acrylamide is a chemical compound found in roasted coffe at temperature above 120⁰C. potential to couse cancer in humans. The coffee used by processed at home in the village of Betara sub-district, Tanjung Jabung Barat, Kuala Tungkal, Jambi. The purpose of this study is to compare acrylamide content traditional coffee powder with the high performance liquid chromatography method (HPLC). The phase of motion used acetonitril : phosphate acid (80:20 v/v), using C18 or oktadesil silica (ODS) with size 250 nm × 4,6 mm,injection volume 20 μl, detector genesys 10S UV-Vis at wavelength 203 nm. Acrylamide is ground coffee was identified at retention time (tR) ± 5,825 minute. This method is proven valid with linearity y = 20717x + 28752, correlation coefficient (r) = 0,998%, the limit of detection 0, 32109 ppm and the limit of quantitation 1,07031 ppm, orecision with

Recently, intensive processing of marine resources has attracted considerable attention. In order to further utilize the byproducts of aquatic shellfish (Pinctada martensii meat) with high value, this study proposes a method of extracting zinc and taurine from P. martensii meat. Zinc was first extracted from P. martensii meat with an ultrasonic crusher, and then taurine was further extracted by ultrasonic-assisted water extraction from the remaining shellfish. After optimization, the biological zinc extraction rate reached 8.63%, and the taurine extraction rate reached 0.71%. Meanwhile, the parameters for cation exchange separation and taurine purification were optimized, in which the injection volume, pH value, and elution rate were set to 8.0 mL, 4.5, and 3.0 mL/min, respectively. Ultimately, the purity the extracted taurine reached 98.16%. This study provides a novel method for the extraction of biological zinc and taurine by deep processing of shellfish meat.

The therapeutic regimen for the treatment of AIDS using efavirenz, lamivudine and tenofovir disoproxil fumarate has demonstrated efficacy and safety. In this work, an analytical method was developed and validated for simultaneous quantitation of efavirenz (EFV), lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) in fixed-dose combination tablet. Analysis by high performance liquid chromatography was performed using a reversed phase column Sun Fire® C18 (250 mm x 4,6 mm; 5 μm) at 30 °C, 20 μL injection volume and detection at 260 nm. The mobile phase, composed of acetate buffer pH 5.4 and methanol, was employed at 1.0 mL/min flow rate and gradient elution. Adequate linearity was obtained in the range from 66 to 198 μg/mL for EFV, 66 to 198 μg/mL from 3TC and 33 to 99 μg/mL for TDF. Relative standard deviation values were lower than 5% and mean recoveries were within 98% to 102%, confirming the precision and accuracy of the method, respectively. In addition, the developed method showed to be selective and robust and can be successfully applied for routine quality control analysis.

A sensitive Ultra-High Performance Liquid Chromatography (UHPLC)-fluorescence method was developed and validated for the determination of ochratoxin-A (OTA) in Turkish wine samples. Naphthalene was used as an internal standard in this study. OTA was separated on a C18 (3.0 mm × 100 mm × 1.8 µm) column and analyses were run under isocratic conditions, with a mobile phase consisting of water/acetonitrile/acetic acid (50:50:1, v/v/v). The flow rate and injection volume were 0.5 ml min−1 and 10 μl, respectively. The excitation and emission wavelengths were 330 nm and 460 nm for OTA, respectively, and 220 nm and 325 nm for internal standard, respectively. A solid-phase extraction (SPE) clean-up procedure on a C18 cartridge was used prior to the analysis of the wine samples by UHPLC. The developed method was validated with respect to linearity, precision, accuracy, limit of detection (LOD), limit of quantitation (LOQ), stability and robustness. The method presented good RSD (< 4 %) and recovery (102.6–105.2 %) values. The LOD and LOQ values were 0.01 ng ml–1 and 0.05 ng ml–1, respectively. All other parameters were acceptable. OTA amounts were found in the range of 2.72‒7.40 µg kg‒1 in the Turkish wine samples.

Background Increasing the reconstitution and injection volumes of abobotulinumtoxinA (aboBoNT-A) could provide more options for aesthetic healthcare professionals. Objective To evaluate efficacy and safety of aboBoNT-A treatment of moderate-to-severe glabellar lines (GL) versus placebo, using a new reconstitution and injection volume. Methods a Materials: In this 6-month, Phase III, randomized, double-blind study, subjects 18-64 years were administered aboBoNT-A 50 U (N=224) or placebo (N=77), as five 0.1-mL-injections (10 U) in the glabellar region following reconstitution of a 300-U-vial in 3 mL. Assessments included time to onset of effect, investigator- (ILA) and subject- (SSA) assessed GL severity, subject satisfaction, aesthetic improvement and safety. The primary endpoint was composite 2-grade response at month 1 (a GL severity of none-or-mild at maximum frown and g2-grade improvement from baseline concurrently on both ILA and SSA). Results Median time to onset was 2 days, 34% of subjects reporting effect on day 1. At month 1, the composite 2-grade responder rate was 65.8% for aboBoNT-A versus 0% for placebo, Pl0.001, 91n92% had none-or-mild GL severity, and 95n100% had a g1-grade GL severity improvement. A g1-grade improvement was sustained in 46-56% of aboBoNT-A-treated subjects up to 6 months (Pl0.001 vs placebo). Aesthetic improvement and subject satisfaction were high throughout 6 months and aboBoNT-A treatment was well tolerated. Conclusion Safety and efficacy of GL treatment using 0.1 mL (10 U) aboBoNT-A per injection site were demonstrated, with rapid onset and up to 6 monthsr duration of effect. Severity improvement was accompanied by sustained aesthetic improvement and subject satisfaction. J Drugs Dermatol. 2021;20(9):988-995. doi:10.36849/JDD.6130.

Purpose To determine the relationship between stopper position and injection volume in aflibercept and ranibizumab prefilled syringes (PFS). Methods Empty aflibercept 2.0 mg PFS and ranibizumab 0.3 mg and 0.5 mg PFS were collected and refilled with saline. The stopper was positioned relative to the preprinted mark and resulting injection volumes were recorded. The position for double the on-label volume was confirmed with repeated testing. The quantitative relationship between position and volume was calculated. Results In ranibizumab PFS, doubling the distance increased the volume injected by 2.6 times. Positioning the stopper 4.0, 3.0, 2.0, and 0 mm proximal to and 1.0 mm distal to the mark injected volumes of 0.13, 0.1, 0.08, 0.05 and 0.03 mL, respectively. The relationship between position (x) and volume (y) was y = 0.019x + 0.048.In aflibercept PFS, doubling the distance increased the volume injected by 3.2 times. Positioning the stopper 2.5, 2.0, 1.0, and 0 mm proximal to and 1.0 mm distal to the mark injected volumes of 0.16, 0.14, 0.11, 0.05 and 0.02 mL, respectively. The relationship between position (x) and volume (y) was y = 0.041x - 0.059. Conclusions Proper positioning of the stopper at the preprinted mark accurately delivers the on-label volume with both the ranibizumab and aflibercept PFS. However, small variations in stopper position appear to have substantial impacts on the volume of drug injected, particularly with the aflibercept PFS.

Many over-the-counter drug products lack official compendial analytical methods. As a result, the United States Pharmacopeia and the United States Food and Drug Administration are seeking to develop and validate new methods to establish analysis standards for the assessment of the pharmaceutical quality of over-the-counter drug products. Diphenhydramine and phenylephrine hydrochloride oral solution, a combination drug product, was identified as needing a compendial standard. Therefore, an ultra-high-performance liquid chromatography method was developed to separate and quantify the two drug compounds and eleven related organic impurities. As part of a robustness study, the separation was demonstrated using different high-performance liquid chromatography systems and columns from different manufacturers, and showed little dependence with changes in flow rate, column temperature, detection wavelength, injection volume and mobile phase gradient. The method was then validated conformant with the International Council for Harmonisation guidelines. For impurities, adequate specificity, linearity, accuracy and precision were demonstrated. For assay, a slight modification to the injection volume was necessary to achieve adequate analytical performance. With successful development and validation, these methods were shown to be suitable for their intended purpose and may be considered for adoption as compendial procedures.

Bath salts, fumigations, cleaners and air fresheners, behind these terms substances are hidden, which count as "Legal Highs". These fancy names are used to pretend Legal Highs as harmless compounds, to circumvent legal regulations for marketing as well as to increase the sales. Besides classic illicit drugs of synthetic origin such as amphetamines, cocaine and MDMA, the trade of these compounds, also known as new psychoactive substances (NPS), is not uncommon today. In many countries, NPS are still not subject to drug control. Among them, there are stimulants such as new amphetamine derivatives or cathinones, which possess a chiral centre. Little is known about the fact that the two possible enantiomers may differ in their pharmacological effect. The aim of this study was to test a novel HPLC column for the enantioseparation of a set of 112 NPS coming from different chemical groups and collected by internet purchases during the years 2010-2018. The CSP, namely Lux® 5 μm i-Amylose-1, LC Column 250 x 4.6 mm, was run in normal phase mode under isocratic conditions, UV detection was performed at 245 nm and 230 nm, injection volume was 10 μl and flow rate was 1 ml/min. With a mobile phase consisting of n-hexane/isopropanol/diethylamine (90:10:0.1), herein, 79 NPS were resolved into their enantiomers successfully, for 37 of them baseline resolution was achieved. After increase of lipophily of the mobile phase to 99:1:0.1, another 27 compounds were baseline separated. It was found that all separated NPS are traded as racemic compounds.

A UPLC-MS method for the estimation of atazanavir sulfate was developed using the “analytical quality by design” approach. The critical chromatographic quality attributes identified were retention time, theoretical plates and peak tailing. The critical method parameters established were percent of organic modifier, flow rate and injection volume. Optimization performed using Box-Behnken Design (BBD) established 10 % organic modifier, 0.4 mL min−1 flow rate and 6-µL injection volume as the optimum method conditions. Atazanavir sulfate eluted at 5.19 min without any interference. Method validation followed international guidelines. The method has proven linearity in the range of 10–90 µg mL−1. Recovery was between 100.2–101.0 % and precision within the accepted limits (RSD 0.2–0.7 %). LOD and LOQ were 2.68 and 8.14 µg mL−1, resp. Stress testing stability studies showed atazanavir sulfate to degrade under acidic and basic conditions. The suggested technique is simple, rapid and sustainable. It is, therefore, suggested for routine analysis of atazanavir sulfate.

For unconventional reservoirs, water flooding performs poorly because of low displacement efficiency; gas flooding shows limited enhanced oil recovery (EOR) capability due to gas breakthrough. Carbonated water injection (CWI) and active CWI (ACWI) are promising EOR methods which combine advantages of water and gas flooding. This paper provides experimental and numerical studies of carbonated water and surfactant injection based on a case study in Changqing Oilfield, China, which is the first time to investigate the feasibility of CWI and ACWI for tight oil reservoirs. This study compares performances of active water injection (AWI), CWI, Water altering gas (WAG), and ACWI. Experimental results reveal that the oil recovery of CWI is 2.7% more than WAG. ACWI achieves the highest incremental oil recovery (9.43%) among four methods. The sensitivity analyses of ACWI + WAG is further implemented experimentally, which demonstrates that ACW as a pre-flood improves 7% of oil recovery during WAG process. For Changqing tight reservoir cores, the optimal injection volume of ACW is 0.8 pore volume. Numerical simulations are conducted to validate the capability of cubic Equation-of-State coupled with Henry's law (EOS/H model) for CWI in tight oil reservoirs, indicating EOS/H model is applicable to correlate phase behavior of carbonated water and oil system. This paper, for the first time, investigates the EOR performance of ACWI in tight oil reservoirs. These results explore the feasible application of using CWI/ACWI in tight oil reservoir development.

Introdução: O p-fenilenodiamina (PPD), amina aromática sensibilizante, vem sendo adicionado ao pó de hena para modificar sua cor natural para preta, aumentando seu tempo de fixação, prática proibida em tinturas para cílios e sobrancelhas. Objetivo: O objetivo deste estudo foi otimizar e validar, em níveis intralaboratoriais, um método analítico por CLAE/UV para identificação e quantificação de PPD em tinturas de hena para cabelos e sobrancelhas. Método: Foi utilizada coluna em fase reversa C8, fase móvel trietanolamina 1% (pH 8,4) e acetonitrila (99:1, v/v), detecção a 280 nm, volume de injeção de 10 μL, fluxo 1,0 mL/min, temperatura da coluna 32°C, tempo de corrida 10 min, linearidade 5-45 μg/mL (n = 5) com coeficiente de correlação de 0,9982. Para o teste de Cochran (homocedasticidade), 0,3350 e o Ccrítico (0,3934), com 99% de confiança. Limites de detecção, 1,17 μg/mL e quantificação, 3,54 μg/mL. O coeficiente de variação da repetibilidade 0,12% e na precisão intermediária pelo teste F obteve-se p-valor de 0,283 com 95% de confiança. Resultados: Os resultados da exatidão compreenderam os critérios de aceitação (90%-107%). Das 19 amostras analisadas, 14 apresentaram teor de PPD entre 1,74% a 3,65% p/p, em desacordo com a Legislação. Conclusões: O método proposto poderá contribuir com o monitoramento da qualidade e segurança de uso destes produtos.

Cell injection plays an important role in genetics, transgenics, molecular biology, drug discovery, reproductive study, and other biomedical fields. Compared with manual cell microinjection and robotic cell microinjection with sole position feedback, force-assisted robotic cell microinjection can improve the success rate and survival rate of cell injection. In this paper, the state-of-the-art research on microinjection of both adherent cells and suspended cells with microforce sensing techniques is reviewed. The significance of force sensors in the robotic cell injection system is also discussed. Five types of prevalent force sensing methods and their applications in cell microinjection are reviewed. The challenges and promising solutions in automating the cell microinjection process are addressed. Note to Practitioners —Microinjection process is a complex task to perform. As the advance progress of high-performance microforce sensors, force-assisted robotic cell injection has been a hot topic in recent years. This paper presents the state-of-the-art survey of recent developments on microforce sensing for robotic cell microinjection to address the research challenges. Based on microforce sensing and control, microinjection of both adherent and suspended cells can benefit from the force-assisted robotic cell injection process. The main challenges and promising solutions in terms of micromanipulator design, injection control design, cell holder design, penetration scheme design, injecting pipette maintenance, injection volume, cost reduction, and microforce sensor calibration issues have been discussed. The related research trends are summarized.

The present study aimed to develop an HPLC method of Cfp analysis which enjoyed highly linearity, repeatability, robustness, ruggedness, selectivity, rapidly, and economic to use. The chromatographic method uses a column Inertsil ODS-3 (250 mm × 4.6 mm × 5 µm). The mobile phase consists of a mixture of acetonitrile: acetate buffer (4:6, v/v) at isocratic flow rate 1.5 mL/min with PDA detector at 240 nm, column oven adjusted at 30 °C, and injection volume 20 µL. The method revealed that satisfied linearity regression R2 (0.9998) with repeatability (0.77%) with LOD and LOQ: 1.102 µg/mL and 3.340 µg/mL respectively. The method showed a successful application of analytical method validation for Cfp in bulk and pharmaceutical formulations.

The objective of the method was to develop a simple, rapid, sensitive, precise, accurate and validated Ultra Performance Liquid Chromatographic (UPLC) method for the estimation of Ticagrelor in tablet dosage form. Chromatographic separation was achieved on an acquity UPLC BDS C8 (150 x 4.6 mm, 5m) column with a mobile phase composed of Buffer 0.1% OPA (2.2 pH) and Acetonitrile in the ratio of 60:40 at a flow rate of 1.0 ml/min and 1 μl injection volume. The effluents were detected at a wavelength of 240 nm using TUV detector. The retention time of Ticagrelor was found to be at 0.942 min. %RSD of the Ticagrelor was found to be 0.7 The method was validated with respect to specificity, accuracy, linearity, precision, robustness. The correlation coefficient for Ticagrelor was found to be 0.999. Recovery of Ticagrelor in formulation was found to be 99.51% . LOD, LOQ values obtained from regression equations of Ticagrelor were 0.45, 1.35 respectively. Due to simplicity, high precision and rapidness the method can be successfully applied for estimation of Ticagrelor in tablet dosage form. Keywords: Ultra Performance Liquid Chromatographic, Ticagrelor, Tablet dosage form.

This study investigates the critical parameters which influence the residual oil recovery by alkaline-surfactant-alternated-gas/CO2 (ASAG) flooding. A series of lab-scale core flood experiments were carried out with sandstone reservoir cores and Assam crude oil to examine the oil recovery potential by various schemes of ASAG flooding. The coreflood results demonstrated that ASAG flooding recovers higher residual oil (23.06% original oil in place, OOIP) compared to surfactant-alternated-gas (SAG: 18.29% OOIP) and water-alternated-gas (WAG: 8.84% OOIP) flooding processes. Effects of key parameters such as injection volume ratio, tapering, reservoir rock property, number of cycles and injection schemes on oil recovery during ASAG flooding were investigated. These factors affect the performance of ASAG flooding to an extent similar to WAG and SAG flooding.

Samryeongbaekchul-san (SBS) is a traditional herbal formula, which is used for the treatment of dyspepsia, chronic gastritis, and anorexia in Korea. To evaluate the quality of SBS decoction by quantifying its main constituents simultaneously using high-performance liquid chromatography coupled with photodiode array (HPLC–PDA) detection, and secondly to determine the antiadipogenic effect of SBS decoction. The main constituents in a 10-μL injection volume of the decoction were separated on Gemini C18 and Luna NH2 columns (both 250 mm × 4.6 mm, 5 μm) at 40 °C using a gradient of two mobile phases eluting at 1.0 mL/min. 3T3-L1 preadipocytes were differentiated into adipocytes for 8 days with or without SBS. After differentiation, accumulated triglyceride contents and leptin production were measured. The correlation coefficients of all constituents in a calibration curve were ≥0.9998 and showed good linearity in the tested concentration range after validation of the method established. The recovery of the four major compounds were 99.46–102.61% with intra- and interday precisions of 0.08–1.01% and 0.15–0.99%, respectively. The four compounds in the lyophilized SBS sample were detected up to 6.46 mg/g. SBS treatment of the differentiated adipocytes significantly inhibited lipid accumulation and leptin production without cytotoxicity. Optimized simultaneous determination of constituents by HPLC–PDA detection will help to improve quality assessment of SBS or related formulas. SBS has an antiadipogenic effect and further investigation to establish the mechanisms of action of its antiadipogenic effect is warranted. Keywords: Antiadipogenic effect, HPLC–PDA, Samryeongbaekchul-san, Simultaneous quantification, Traditional Korean medicine

A new simple, rapid and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed by employing Quality by Design (QbD) approach for determination of levetiracetam and pyridoxine HCl in prepared tablets. Levetiracetam and pyridoxine HCl are co-administered because treatment with the antiepileptic levetiracetam leads to a deficiency in pyridoxine HCl. Fractional factorial design (FFD) was applied for screening of the four independent factors: pH of the aqueous part of the mobile phase, flow rate, injection volume and % of the organic modifier. Analysis of variance (ANOVA) confirmed that the four factors were significant. Optimization of the chromatographic conditions was performed using central composite design (CCD). The Analysis was achieved on BDS Hypersil C8 (250 × 4.6 mm, 5 μm) column applying an isocratic mobile phase containing MeOH and 25 mM KH2PO4 buffer pH 3 (38.4:61.6, v/v) at 0.8 mL/min flow rate with UV detection at 214 nm and 5 μL injection volume. The proposed method was validated according to ICH guidelines. Under optimized conditions, linear ranges of 1.56–100 μg/mL and 0.39–100 μg/mL were obtained for levetiracetam and pyridoxine HCl, respectively, with correlation coefficients (R2) of 0.999. The average recoveries ranged from 95.46 to 101.14%. The inter- and intra-day precisions were lower than 1%. The proposed method showed good predictability and robustness.

Cervical dystonia (CD) is primarily treated with botulinum toxin, at intervals of ≥ 12 weeks. We present efficacy, patient-reported outcomes (PROs), and safety in adults with CD at the last available visit after a single set of abobotulinumtoxinA (aboBoNT-A) injections versus placebo using 500 U in a 2-mL injection volume. In this 12-week, randomized, double-blind trial, patients were ≥ 18 years of age with primary idiopathic CD, had a Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score ≥ 20, and TWSTRS-Severity subscale score > 10 at baseline. Patients (N = 134) were randomized (2:1) to aboBoNT-A (n = 89) or placebo (n = 45), with aboBoNT-A patients treated with 500 units (U) if toxin-naïve, and 250 to 500 U based on previous onabotulinumtoxinA dose if non-naïve. Endpoints included total TWSTRS, Pain Numeric Rating Scale (NRS-Pain; 24-hour), Treatment Satisfaction Questionnaire for Medication, and other PROs for pain, depression, and global health. Results are for the intent-to-treat population, with “Week 12” (Wk12) comprising the last available post-baseline assessment (end-of-study or early withdrawal). Mean TWSTRS total scores improved from 42.5 at baseline to 35.4 at Wk12 with aboBoNT-A and 42.4 to 40.4 with placebo (treatment difference: –4.8; 95% confidence interval [CI]: –8.5, –1.1; p = 0.011). At Wk12, mean (95% CI) change from baseline in NRS-Pain was –1.0 (–1.59, –0.45) for aboBoNT-A and –0.2 (–0.96, 0.65) for placebo. AboBoNT-A demonstrated numeric improvements in other PROs. More aboBoNT-A–treated patients than patients receiving placebo reported being at least “somewhat satisfied” with treatment (60.4% vs 42.2%, respectively), symptom relief (57.0% vs 40.0%), and time for treatment to work (55.8% vs 33.3%). No new adverse events were reported. Results indicate that in patients with CD, treatment with aboBoNT-A using a 2-mL injection provided sustained improvement in the TWSTRS total score and patient-perceived benefits up to 12 weeks. Trial registration: Clinicaltrials.gov Identified: NCT01753310.

In two-dimensional liquid chromatography, the combination of hydrophilic interaction liquid chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) is very attractive due to the complementarity of their separation mechanisms. On-line comprehensive HILIC x RPLC is well-known to give rise to a large retention space coverage when dealing with ionisable compounds. However, method development in on-line HILIC x RPLC is challenging due to the reversed solvent strength between both dimensions, which can greatly affect the peak shapes in the second RPLC dimension, and thus the separation quality and the method sensitivity. In the present contribution, we compared four strategies designed to avoid this problem: (1) flow splitting, which consists in reducing the injection volume in the second dimension (2D), (2) on-line dilution with a make-up flow and (3) on-line dilution with Active Solvent Modulation (ASM), which both consist in reducing the solvent strength of the injected fractions, and (4) Total Breakthrough Strategy, which we recently proposed. Unlike the three preceding strategies, this latter one consists in injecting large volumes of strong solvent in 2D. The performance of each strategy was evaluated for sub-hour separations of a tryptic digest in on-line HILIC x RPLC. In this work, we considered the critical case for which the same column internal diameters (i.e. 2.1 mm here) are used in both dimensions. Peak capacity, peak shapes and peak intensities were considered for this evaluation. The highest peak capacity could be achieved with Total Breakthrough Strategy while the lowest one with on-line dilution using ASM. Peak intensities were usually higher with on-line dilution approaches (make-up flow and ASM). However, despite the presence of breakthrough, peak intensities were approximately 7-fold higher with Total Breakthrough Strategy than with flow splitting.

In Japan, two 0.4% sodium hyaluronate (HA)-based submucosal injection materials (SIMs) are currently used in endoscopic submucosal dissection (ESD): MucoUp (HA-Mc) and Ksmart (HA-Ks). HA-Mc and HA-Ks have the same concentration and are, thus, construed by most endoscopists to have no difference. Nevertheless, visual observation conveys the impression that HA-Ks have a higher viscosity than HA-Mc, suggesting that HA-Ks performs better than HA-Mc. This study aimed to examine the differences between HA-Mc and HA-Ks. HA-Ks exhibited higher viscosity due to greater weight-average molecular weight compared with HA-Mc. HA-Ks had significantly greater submucosal elevation height (SEH) than HA-Mc; the SEH of HA-Ks-80% (80% dilution of HA-Ks) was the same as that of HA-Mc. The ESD procedure time was significantly shorter with HA-Ks than with HA-Mc (15.2 ± 4.1 vs. 19.5 ± 5.9; P = 0.049). The total injection volume for HA-Ks was significantly lower than that for HA-Mc (10.8 ± 3.6 vs. 14.4 ± 4.6; P = 0.045). However, no significant difference in these items was observed between HA-Mc and HA-Ks-80%. HA-Mc and HA-Ks were considered to be almost the same. Nonetheless, HA-Ks exhibited higher viscosity and SIM performance than HA-Mc. HA-Ks-80% had almost the same performance as HA-Mc. Thus, understanding SIM performance and characteristics requires a focus on the viscosity of SIMs.

To the Editor We read with great interest the brief technical report ‘Opening injection pressure monitoring using an in-line device does not prevent intraneural injection in an isolate nerve model’ by Mejia et al .[1][1] We do concur with their findings but believe that a clarification should

Injection of biological molecules into the intravitreous humor is of increasing interest for the treatment of posterior segment eye diseases such as age-related degenerative macular degeneration. The injection volume is limited by an increase in intraocular pressure (IOP) and 50–100 µL are typically used for most intravitreally (IVT) applied commercial products. Direct measurement of IOP is difficult and has not been studied dependent on solution properties and injection rates. We used an instrumental set-up to study IOP ex vivo using healthy enucleated porcine eyes. IOP was determined as a function of injection volume for viscosities between 1 and 100 mPas, injection rates of 0.1, 1, and 1.5 mL/min, and needle length and diameter (27/30G and 0.5/0.75″) using Dextran solutions. IOP increased exponentially for injection volumes larger than 100 µL. We did not observe differences in IOP dependent on viscosity, injection rate, and needle diameter. However, variability increased significantly for injection volumes larger than 100 µL and, unexpectedly, declined with higher viscosities. We demonstrate that the exponential increase in IOP is not reflected by injection force measurements for typical configurations that are used for IVT application. The present findings may guide injection volumes for intravitreal injection and inform injection force considerations during technical drug product development.

Gas injection volume is the key parameter of air drilling with raise boring machine, and the determination of the minimum gas injection volume is one of the key technologies to improve the drilling speed and shorten the drilling period. Based on the characteristics of raise boring technology, the construction technique of raise boring with air as circulating medium is studied, and the double-channel structural characteristics of direct circulation system are discussed. On the basis of summarizing and analyzing the principle and characteristics of the calculation methods, the minimum gas injection volume required for rock carrying in the engineering of air drilling with raise boring machine is calculated by using the minimum velocity method. The research results provide a basis for the design of drilling parameters and are of great significance for expanding the application range of raise boring method and realizing the safe and rapid construction of shaft.

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%, all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 &mu, L, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

China has abundant tight oil resources, but due to the unsolved energy supplement problems, the low production and low efficiency of multi-staged fracturing horizontal wells in tight oil reservoirs are very serious, how to solve these problems has become the key to the efficient development of tight oil resources in China. In this article a set of “energy storage tank” device was innovatively designed to simulate infinite formation and CO2 huff and puff experimental research of tight oil reservoir was carried out. An indoor experimental scheme was developed based on the field production parameters and the effects of three key factors: CO2 huff and puff cycle, injection volume, and soak time on the recovery of CO2 huff and puff were analyzed. The experimental results show: a non-uniform distribution of the remaining oil around the fractures in the core was observed after the huff and puff experiment. Remaining oil at the core end connected to the “energy storage tank” was relatively less; during the process of CO2 huff and puff, with the increase of CO2 injection, the range of interaction between CO2 and oil extends to the depth of the reservoir. The oil replacement efficiency by CO2 is lower than that without using “energy storage tank” during the process of the flowback. Huff and puff recovery is mainly concentrated in the first three cycles; under the same huff and puff conditions, the longer the soak time is, the higher the huff and puff recovery is, but with the increase of soak time, the increase of recovery decreases. The “energy storage tank” device designed in this paper can realistically simulate the actual CO2 huff and puff process in infinite formation, which overcomes the disadvantages of the existing indoor CO2 huff and puff experiments and improves the experimental accuracy.

A low permeable sand conglomerate condensate gas reservoir in Bohai Sea has a high content of condensate oil and a small pressure difference between the ground and the dew point. When it is put into operation, the formation will be blocked by retrograde condensate, resulting in the loss of condensate oil. In order to find out the specific measures to improve the recovery of condensate, the effect of injection timing and volume on oil displacement efficiency was analyzed by long core cyclic gas injection experiment, and then the timing and volume of gas injection were optimized by numerical simulation. The long core cyclic gas injection experiment shows that the oil displacement efficiency of gas injection under the original formation pressure is much higher than that of gas injection under the condition of depletion to the maximum reverse condensate pressure; the oil displacement efficiency of gas injection under the original formation pressure increases with the increase of injection volume, but the increase of oil displacement efficiency decreases after gas channeling. The optimization results of numerical simulation also show that: for this kind of high condensate gas reservoir with near dew point pressure, initial gas injection and increasing injection volume are beneficial to improve the recovery ratio of condensate oil; compared with the recovery ratio of 16% for exhausted development of condensate oil, the recovery ratio of condensate oil for 100% reinjection can reach 32.78%. Through the long core cyclic gas injection experiment and numerical simulation optimization, the optimal gas injection strategy will be directly used to improve the recovery of condensate in this condensate gas reservoir.

Endemic in more than 90 countries and territories, malaria is the most widely, populational, and geographically, parasitic disease in the world. Plasmodium sp. resistance to available drugs is one of the biggest problems for malaria eradication. In this study, we develop a method for the simultaneous determination of two new derivatives of betulinic and ursolic acids with antimalarial activity designated 3-O-butanoylbetulinic and 3-O-butanoylursolic acids. An analytical method was developed by high-performance liquid chromatography coupled, in series, to ultraviolet (UV) and charged aerosol (CAD) detectors. The chromatographic system, operated isocratically by reversed-phase, consisted in a mobile phase composed of acetonitrile: water pH 3.0 adjusted with formic acid (85:15, v/v), flow rate of 1.2 mL/min and a PhenoSphere Next octadecylsilane column (250 mm x 4.6 mm, 5 μm particle size). Chromatograms were recorded simultaneously in UV and CAD, at a concentration of 50 µg mL-1, an injection volume of 20 μL at a controlled temperature of 50 °C. The method was found to be selective, linear (r > 0.99), precise (RSD < 2.0%), accurate, and robust for both analytes, and considered statistically validated, and can be applied to the identification and quantification of these new drug candidates.

In order to find out the main factors influenced the hatchability and improve the hatchability of the windowed chicken eggs at stage X, several experiments were made on the basis of the former patent of eggshell windowing methods on equatorial plane, such as cutting and sealing techniques, air cell recovering, laying position immediately after sealing, as well as the injection volumes into the subgerminal cavity of the blastoderm. The result showed that:1) the best sealing material combination was straw powder (SP) and instant glue (IG); 2) there was a highly positive correlation between air cell rate and hatchability; 3) the highest hatchability increased to 71.6% when the eggs were windowed and sealed with IG dropped firstly and then SP sprinkled, finally lay down with the blunt end upward immediately after being sealed; 4) the hatchability was significantly reduced as injection volume (DMEM) was increased (p

In this work, high-performance thin-layer chromatography (HPTLC) coupled with multivariate image analysis (MIA) is proposed as a fast and reliable tool for authentication and adulteration detection of Iranian saffron samples based on their HPTLC fingerprints. At first, the secondary metabolites of saffron were extracted using ultrasonic-assisted solvent extraction (UASE) which was optimized using central composite design (CCD). Next, the RGB coordinates of HPTLC images were used for estimation of saffron origin based on principal component analysis (PCA). The PCA scores plot showed that saffron samples were clustered into two clear-cut groups which was 92% matched with the geographical origins of the samples. In the next step, common plant-derived adulterants of saffron including safflower, saffron style, calendula, and rubia were investigated with MIA analysis of HPTLC images using partial least squares-discriminant analysis (PLS-DA) at 5-35% (w/w) levels. The PLS-DA results showed proper classification of saffron and adulterants with sensitivity 99.14%, specificity 96.94%, error rate 1.96% and accuracy 98.04. Also, the effect of HPTLC injection volume on the performance of the proposed strategy was evaluated. The ability of the proposed method was then investigated by analyzing two additional sample sets including mixed samples of four plant-derived adulterants and adulterated commercial samples. Sensitivity and specificity of this model were 100% which confirmed its validity.

This study proposed a novel analytical method for the separation and determination of cobalamin and cobalt in kefir samples by high performance liquid chromatography-inductively coupled plasma-optical emission spectrometry (HPLC-ICP-OES) in addition to determination of cobalamin in HPLC system. Chromatographic parameters such as column type, buffer solution, mobile phase flow rate and sample injection volume were individually studied and optimized. In addition, cobalamin was simultaneously determined by high performance liquid chromatography with ultraviolet detection (HPLC-UV). LOD values of cobalt in cobalamin and cobalt for HPLC-ICP-OES system were calculated as 0.07 mg/kg (as Co) and 0.06 mg/kg, respectively. Recovery studies were conducted to evaluate the accuracy/applicability of the method. Recovery results for cobalt in cobalamin and cobalt detected by the HPLC-ICP-OES system were calculated in the range of 87.4–100.1 and 98.8–115.0%, respectively while recovery results for cobalamin were found to be between 89.2 and 98.3% for HPLC-UV system.

When using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) to quantify In Vivo samples, an internal standard (ISTD) is key in correcting for variability within the sample extraction process and injection volume. Just as important is the ability of the internal standard to identify any matrix effects, which can artificially suppress or enhance the signal of the compound of interest. To properly do this, the internal standard should co-elute with the compound. A common source of potential matrix effects with In Vivo studies is from the excipient(s) used to formulate the compound for dosing. In the world of high-throughput discovery bioanalysis, a lab can quantitate over a hundred compounds each week, many of which are evaluated once, and rarely is a stable-isotope labeled (SIL) internal standard available (the industry gold standard). Finding a suitable and easy-to-use alternative LC-MS/MS method is important to providing high quality data. To overcome this challenge, a homologous series of compounds was synthesized to improve the chromatographic range for co-eluting ISTD's. This novel mix of internal standards was shown to have key characteristics making it ideal for use as a near universal internal standard mix including but not limited to: they ionize in both positive and negative modes, they are susceptible to signal perturbation from common formulation excipients, and they cover a wide range of retention times.

To analyze the water/polymer co-flooding seepage law in offshore oilfields, we took the Jinzhou 9-3 oilfield as an example, analyzed the dynamic characteristics of water/polymer co-flooding, and then applied streamline simulation and tracer simulation technology to obtain the water/polymer co-flooding seepage law. The interference degree of the water/polymer co-flooding was quantified, and the accuracy of the seepage law was tested. Finally, a reasonable polymer injection volume was obtained using the economic law. The results demonstrated that the water-cut of the Jinzhou 9-3 oilfield in the water/polymer co-flooding stage was high, the annual decrease of polymer store ratio increased by 2.02 times, and the swept area of polymer was limited to some extent. Mutual interference existed in the water/polymer flooding, and the oil increment of per ton polymer decreased by 36.5%. In the late stage of the water/polymer co-flooding, the utilization rate of water and polymer was low, and the plane swept area and vertical swept volume were small. If the oil price was 50 dollars/bbl, when the output-input ratio was set at 1, the reasonable polymer injection volume was 0.59 PV, and the continuous polymer injection volume was 0.29 PV in the water/polymer co-flooding stage. The study results could improve the development benefit of the Jinzhou 9-3 oilfield, and they could also provide the references for the development of the same type oilfield.

Summary Objectives The main objective of the present study was to develop and validate simple, precise, sensitive and accurate RP-HPLC method for the simultaneous estimation of docetaxel (DTX) and ritonavir (RTV) in PLGA nanoparticles (PLGA-NPs). Methods The DTX and RTV co-loaded PLGA-NPs were developed by the nanoprecipitation technique. The RP-HPLC method was developed by using (Agilent Compact LC-1220) and Zorbax Eclipse plus C18 column (150 × 4.6 mm, 3.5 μm, Agilent). Finally, the developed method was validated according to the international conference on harmonization (ICH) guidelines. Results The chromatographic separations of DTX and RTV with good resolutions have been achieved by using the mobile phase Acetonitrile: Water (60:40 v/v) containing 0.1% v/v of orthophosphoric acid at a flow rate of 1.0 mL/min, injection volume of 25 μL, and at 239 nm wavelengths. The validated method found to be linear in the range of 0.001–100 μg/mL for DTX and RTV. Detection and quantification limits for DTX were found to be 0.7 and 2.31 μg/mL respectively and for RTV it is 0.3 and 2.87 μg/mL respectively. The % RSD was found to be less than 2% revealing the precision of the developed method. Besides, the recovery rate was observed close to 100% for both the drugs confirming the accuracy of the method. Minor alterations in the chromatographic conditions have revealed robustness and ruggedness of the developed method. Conclusion The developed analytical method is simple, precise, sensitive, and reproducible which can be used for the simultaneous estimation of DTX and RTV in the PLGA-NPs.

Estimation of injection volume during a preparative chiral separation can be challenging. Commonly one attempts to maximize the injection volume to reduce total separation time. The factors that limit increasing injection volume are (a) purity constraint(e.g. enantiomeric excess) and (b) criterion of product recovery. Standard industrial practice is to successively inject increasing volume of sample mixture until two adjoining peaks (e.g. peaks of two enantiomers) touch respective baselines. Separation scientists may spend considerable time and material to detect this injection volume before starting the stack-injection run. This increased method-development time increases time spent on the instrument, resulting in decreased efficiency. In this report we demonstrate the utility of a mathematical model-based approach that can be employed for faster estimation of this optimum injection volume. Note that the model does not intend to detect the theoretical maximum injection volume, rather tries to mimic the experimental optimization approach through simulation. The method requires experimental data from one initial trial run as input to predict the final "optimum" injection volume, thus saving time and material compared to situations that require multiple trial runs. The proposed model is simple enough to be implemented in a Microsoft Excel spreadsheet, but offers reasonably accurate estimation. Although the example presented in this report is of preparative separation of a racemic mixture with supercritcal fluid chromatography (SFC), in general the model is applicable to any preparative separation under isocratic conditions where the chromatographic peak follows Langmuir adsorption isotherm behavior. A description of the fundamental basis of the model is presented here along with experimental results that demonstrate its utility.