ESTIMATION OF RESIDUAL SOLVENTS IN NETUPITANT API BY HEADSPACE GAS CHROMATOGRAPHY

Objective: Residual solvents are undesirable components present in Active Pharmaceutical Ingredients (API), excipients, or drug products. To meet the specific quality-based requirements, the presence of these solvents in pharmaceutical products should be monitored to ensure their safety. The main objective of this work is to develop a new method for the determination of residual solvents in netupitant API by an HS-GC method with an FID detector. Methods: An automated headspace GC method has been developed and validated for the estimation of the residual solvents-N-methyl pyrrolidine, xylene, toluene, and N, N Dimethylacetamide in netupitant API. The samples were dissolved in dimethyl sulfoxide and the equilibrium headspace gas was formed at 80 ᵒC, which was analyzed using a DB-624 column (30m*0.53 mm, 3.00 µm) with an injector and detector temperature set at 160 ᵒC and 230 ᵒC, respectively. The initial oven temperature was set at 60 ᵒC for 5 min and programmed at a rate of 10 ᵒC/min to the final temperature of 150 ᵒC, with a hold time of 5 min by maintaining the flow rate of 4.0 ml/min with a split ratio of 1:10, and total run time of 20 min. Nitrogen was used as carrier gas. The method developed was validated as per International Conference for Harmonization (ICH) guidelines for repeatability, linearity, range, ruggedness, detection limit, quantification limit, and recovery studies. Results: The linearity range selected was 50-350µg/ml and the correlation coefficient(γ2) values for all the solvents were found to be>0.99; recovery studies values were in a range of 90-110% and %RSD values were also found to be not more than 10 for the solvents. Conclusion: A novel, accurate, sensitive, and simple method was described for estimating residual solvents in Netupitant API by Headspace Gas Chromatography (HS-GC) coupled with a Flame Ionization Detector (FID). Excellent results have been observed for all the validated parameters with good peak resolution and lesser retention times.

Simultaneous Determination of the Five Constituents in Maiwei Dihuang Pills by the HPLC-DAD Method

Objective. The purpose of study is to establish an HPLC-DAD method for determination of the five constituents (deoxyschizandrin, γ-schizandrin, loganin, paeoniflorin, and paeonol) in Maiwei Dihuang Pills. Methods. An Agilent ZORBAX SB-C18 chromatographic column was carried out to determine the five constituents of 50% methanol extract of Maiwei Dihuang Pills. Results. It was found the chromatographic peak resolution of each component in the study sample solution was 1.5 higher than that of other peaks and no peaks appeared in the blank control solution during the same time, suggesting specificity of HPLC-DAD was well established. The linearity test indicated that deoxyschizandrin, γ-schizandrin, loganin, paeoniflorin, and paeonol were 11.6–72.3 μg/mL, 6.4–45.2 μg/mL, 35.2–237.6 μg/mL, 18.1–114.2 μg/mL, and 32.2–215.3 μg/mL, respectively, suggesting each component has a good linear relationship within its own range. Additionally, the precision of HPLC-DAD was confirmed by a precision test; the stability of the study sample solution was confirmed by a stability test; and good reproducibility of HPLC-DAD was proved by a reproducible test. The recovery rate test showed that relative standard deviation (RSD) of recovery rate in deoxyschizandrin, γ-schizandrin, loganin, paeoniflorin, and paeonol was 100.26% (1.80%), 101.39% (1.74%), 101.19% (1.76%), 102.50% (1.65%), and 102.30% (1.58%), respectively. Conclusions. HPLC-DAD used to determine the five constituents in Maiwei Dihuang Pills, and it was easier and faster to operate, showing good condition in repeatability, precision, stability, and recovery, which is a great option for quality control.

Development of a Novel, Fast, Simple HPLC Method for Determination of Atorvastatin and its Impurities in Tablets

Our main target and concept was to develop a method for the determination of the most prescribed antilipemic drug, atorvastatin, together with its related substances, with a single sample preparation and during a single chromatographic run, in the shortest possible period of time, with the lowest possible mobile phase consumption. A new rapid, simple chromatographic method for the determination of atorvastatin and its main specified impurities was developed, using different chromatographic columns. With this new concept of a mobile phase and a powerful core–shell, or a superficially porous silica-based column, satisfactory results for targeted parameters, such as critical peak resolution, run time length, and column backpressure, were achieved. The analysis is performed within a run duration of less than 15 min, which is about six times shorter than the official European Pharmacopoeia method. The chromatogram performances suggests that the method limit of quantification (LOQ) can be about 7 times lower, and the limit of detection (LOD) about 20 times lower, using an injection volume of only 2 µl. This was confirmed by the performed method validation in accordance with the International Conference on Harmonization (ICH) guideline for the validation of analytical procedures Q2(R1), where the selectivity, linearity, accuracy, precision, limit of quantification, and limit of detection were tested and confirmed.

Bismuth/Porous Graphene Heterostructures for Ultrasensitive Detection of Cd (II)

Heavy metals pollution is one of the key problems of environment protection. Electrochemical methods, particularly anodic stripping voltammetry, have been proven a powerful tool for rapid detection of heavy metal ions. In the present work, a bismuth modified porous graphene (Bi@PG) electrode as an electrochemical sensor was adopted for the detection of heavy metal Cd2+ in an aqueous solution. Combining excellent electronic properties in sensitivity, peak resolution, and high hydrogen over-potential of bi-continuous porous Bi with the large surface-area and high conductivity on PG, the Bi@PG electrode exhibited excellent sensing ability. The square wave anodic stripping voltammetry response showed a perfect liner range of 10−9–10−8 M with a correlation coefficient of 0.9969. The limit of detection (LOD) and the limit of quantitation (LOQ) are calculated to be 0.1 and 0.34 nM with a sensitivity of 19.05 μA·nM−1, which is relatively excellent compared to other carbon-based electrodes. Meanwhile, the Bi@PG electrode showed tremendous potential in composite detection of multifold heavy metals (such as Pb2+ and Cd2+) and wider linear range.

An Easy Efficient Method of Veterinary Drug Residue Analysis in Raw Milk by RP-HPLC-UV with Application to Raw Milk

Background: This study reports an easy method of a veterinary drug investigation in raw milk, based on QuECHERS extraction followed by RP-HPLC-UV analysis. Use of this benchtop system was motivated by its availability and moderate cost relatively to other sophisticated methods such as LC-MS which are more efficient. Methods: This developed method has been optimized and then after validation according to EU legislation, it demonstrated good linearity with R²>0.997, acceptable peak resolution within a short time (<9.5 min) and good recovery of the analyzed drugs (OXY, ALZ and IVR, respectively 87.08, 99.02 and 92.01 %). Additionally, we applied the method to the analysis of cow milk, collected in Nouakchott, capital of Mauritania. Results: The obtained results indicated a mixed level of drug use according to targeted molecules. In 42% of sampled farms, the anti-parasitics IVR and ALZ were detected whereas the antibiotic OXY was detected in 50%. Conclusion: This investigation shows that 17% of the sampled farms exceeded European standards for IVR drug.

Separation of Fatty Acid Ethanolamides using High Performance Liquid Chromatography

This study aimed to separate fatty acid ethanolamides (FAE) through an enzymatic reaction of ethanolamine and the Terminalia catappa (Local name: Ketapang) seed oil by using reverse-phase high-performance liquid chromatography (RP-HPLC). A 4.6 mm × 150 mm, 5 μm SunFire C18 column was used. Separation optimization was performed by analyzing different variables, which includes mobile phase composition (acetonitrile/water), flow rate and sample concentration. The separation results showed that the retention time for all components was 4.5; 2.4; 12.9; and 6.3 min for fatty acid ethanolamides: oleoylethanolamide, linoleoylethanolamide, stearyl diethanolamide and palmitoylethanolamide, respectively. Inter-peak resolution of >1.5 indicated that each component was accurately separated.

A rapid HPLC method for the determination of lactoferrin in milk of various species

This Research Communication describes the adaptation and testing of an RP-HPLC method, previously tested for the determination of lactoferrin (LF) in whey, for its applicability to determine milk lactoferrin content. Milk samples of various species, namely, ovine, caprine, bovine, donkey and human milk, were tested. The advantage of this RP-HPLC method includes speed and convenience, as it does not include extensive pretreatment or separation steps. A simple pre-treatment step was added in order to remove fat and proteins of the casein family and the samples were tested. The results varied in terms of elution of the LF peak both between the milk of the different species as well as from the initial application on whey. The peak resolution was satisfactory in the cases of ovine, bovine and donkey milk samples while for caprine and human milk an interference with other peaks was observed. Nevertheless, quantification of LF was found possible for all samples. This new application of the modified method will allow the determination of LF in milk samples of the tested species either for everyday analysis or as a useful qualitative screening for presence or absence of LF.

Pyrolitic Graphite Mosaic Crystal Thickness and Mosaicity Optimization for an Extended Source Von Hamos X-ray Spectrometer

Bragg spectroscopy, one of the best established experimental techniques for high energy resolution X-ray measurements, has always been limited to the measurement of photons produced from well collimated (tens of microns) or point-like sources; recently, the VOXES collaboration at INFN National Laboratories of Frascati developed a prototype of a high resolution and high precision X-ray spectrometer working also with extended isotropic sources. The realized spectrometer makes use of Highly Annealed Pyrolitic Graphite (HAPG) crystals in a “semi”-Von Hamos configuration, in which the position detector is rotated with respect to the standard Von Hamos one, to increase the dynamic energy range, and shows energy resolutions at the level of 0.1% for photon energies up to 10 keV and effective source sizes in the range 400–1200 μ m in the dispersive plane. Such wide effective source dimensions are achieved using a double slit system to produce a virtual point-like source between the emitting target and the crystal. The spectrometer performances in terms of reflection efficiency and peak resolution depend on several parameters, among which a special role is played by the crystal mosaicity and thickness. In this work, we report the measurements of the Cu(K α 1 , 2 ) and the Fe(K α 1 , 2 ) lines performed with different mosaicity and thickness crystals in order to investigate the influence of the parameters on the peak resolution and on the reflection efficiency mentioned above.