Degradation Profiling of Lisinopril and Hydrochlorothiazide by RP- HPLC method with QbD Approach

RP-HPLC method was developed for the estimation of Lisinopril and Hydrochlorothiazide in tablet dosage form with the help of Quality by Design (QbD) approaches. In this method concentration of each drug was obtained by using the absorptivity values calculated for drug wavelength 226.0 nm and solving the equation. The RP-HPLC method was performed C18-(100mm x 4.6 mm,)2.5 μm particle size in gradient mode, and the sample was analysed using methanol 45.0 ml and 55.0 ml (pH 3.3 0.05% OPA with TEA) as a mobile phase at a flow rate of 0.8 ml/min and detection at nm. By the retention time for Lisinopril and Hydrochlorothiazide found 3.39 and 4.59 min respectively. Validation related the method is specific, rapid, accurate, precise, reliable, and reproducible. Calibration plots by both HPLC were linear over the 5-25 and 12.5-62.5 μg/ml for Lisinopril and Hydrochlorothiazide respectively, and recoveries from tablet dosage form were between 99.02 and 100.00 %. The method can be used for routine of the quality control in pharmaceuticals. The degradation profiling of Lisinopril and Hydrochlorothiazide were also carried out.

Pharmacokinetic study of hypaphorine, a potential agent for treating osteoclast-based bone loss, on rats using LC-MS/MS

Aim and Objective: A high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of hypaphorine, a potential agent for treating osteoclast-based bone loss, was developed and valadated in rat plasma. Materials and Methods: Plasma samples were pretreated by the protein precipitation. Chromatographic separation was performed using an Inertsil ODS-3 column (50 mm × 4.6 mm, 5 μm). The mobile phase consisted of water (containing 0.1% formic acid) and acetonitrile in a gradient mode at a flow rate of 0.5 mL/min. The acquisition was carried out in selected reaction monitoring (SRM) of the transitions from protonated precursor ion [M + H]+ to the particular daughter ion and the mass transitions of hypaphorine and IS were 247 → 188 and m/z 219 → 188, respectively. The method was validated in terms of selectivity, linearity, accuracy and precision, extraction recovery and matrix effect, stability and carryover. Results: It showed good linearity over the range of 1-2000 ng/mL (R2 = 0.9978). The intra-batch accuracy was within 93.95-105.81% and the precision was within 4.92-11.53%. The inter-batch accuracy was within 96.18-100.39% with a precision of 6.22-11.23%. The extraction recovery and matrix factors were acceptable. Conclusion: The simple and rapid method was successfully applied to the pharmacokinetics study in rats following oral administration of hypaphorine at the doses of 0.5, 1.5, and 4.5 mg/kg.

Separation and Determination of Process Related Impurities in Palbociclib: A Rp-hplc Study

Aims: A new gradient RP-HPLC method was developed for the separation and determination of process related impurities in Palbociclib. Methodology: The chromatographic separation was achieved on a Inert sustain swift (C18) column using a mobile phase comprising of perchloric acid and acetonitrile in a gradient mode at a flow rate of 1 mL/min. over a runtime of 50 minutes. All the eluants were monitored at 230 nm. The optimized method was validated as per ICH guidelines for various parameters. Results: The linearity of the method was proposed in the range of LOQ to 250 % for the drug and its impurities by subjecting the data obtained to statistical analysis using correlation coefficient model (r > 0.99). The method also gave acceptable recovery of all the four impurities at each level and was found to be accurate. The % RSD obtained in the method precision and intermediate precision were less than 2% depicting the precision of the method. The LOD and LOQ values were calculated based on the signal to noise ratio and are indicating the sensitivity of the method. The specificity of the method was checked in the presence of process related impurities and also degradants generated by exposing to a variety of forced degradation conditions. Conclusion: The proposed RP-HPLC method for the determination of process related impurities of Palbociclib could be routinely used in the quality control testing.

A Simple and Sensitive LC-MS/MS Method for Determination and Quantification of Potential Genotoxic Impurities in the Vismodegib Active Pharmaceutical Ingredient

A rapid and sensitive LC-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative analysis of four potential genotoxic impurities Imp-A (2-chloro-5-nitroaniline), Imp-B (1-chloro-2-iodo-4-nitrobenzene), Imp-C (1-(2-chloro-5-nitrophenyl)ethan-1-one) and Imp-D (2-chloro-5-nitrobenzoic acid) in Vismodegib API drug sample. This trace analysis was achieved on CSH C18, 15.0 cm x 3.0 mm, 1.7 micron column maintained at 45°C. Optimal mobile phase consisted of 0.05% formic acid in water was used as mobile phase A and acetonitrile used as mobile phase B in gradient mode with the flow rate of 0.5 mL/min. The developed method had the short run time of 12 minutes. Quantification of four potential genotoxic impurities were carried out using mass detection with electrospray ionization in multiple reaction monitoring mode. The method was linear in the range of 0.03 ppm to 1.50 ppm for four potential genotoxic impurities with a correlation coefficient not less than 0.999. The recoveries were found satisfactory over the range between 96.67 and 106.90% for all selected impurities. The developed method was able to quantitate all four PGIs at a concentration level of 0.03 ppm (0.03 ppm with respect to 20 mg /mL Vismodegib).

Temperature Field and Gradient Effect of a Steel-Concrete Composite Box Girder Bridge

To study the effect of the temperature field and gradient of a steel-concrete composite box girder bridge, a 5 × 35 continuous composite box girder bridge is used as the research object. The temperature measuring point is set by selecting a typical cross section, and the temperature change data are measured. The temperature field of the different positions in the composite box girder bridge is studied, the global and local temperature differences are compared, and the law of temperature distribution and the main factors affecting the temperature field are formulated. The most unfavourable expression function of the vertical temperature gradient of the section is simulated using the measured data, the existing standard temperature gradient mode is compared, the finite element model of the bridge is established, and the influence of the actual temperature gradient mode on the stress and deformation of the composite girder is further analysed. The conclusions show that the temperature differences of different azimuth sections and the local temperature differences between the steel and concrete joint parts of the steel-concrete composite box girder bridge are not significant. The temperature gradient heating and cooling model fitted by the measured temperature field can be used as a reference for the structural design of similar local bridges.

Investigation of Drug-Excipient Compatibility Studies Using Validated RP-HPLC Method for Azelnidipine and Telmisartan Tablets

Aims: The Drug-Excipient compatibility testing was conducted at an early product development stage to determined that Excipients were compatible with drugs used in formulation and to distinguish as many degradation products as possible using validated gradient RP-HPLC method. Study Design: Drug-Excipient Compatibility study was conducted in glass vials at different stability conditions namely, at 300C + 20C/75% + 5% RH, 400C + 20C/ 75% + 5% RH for 04 weeks and another set of closed vials were stored in stability chamber at temperature 600C + 20C for 02 weeks. Methodology: Samples were analyzed by validated RP-HPLC method using Inertsil C-18 Column 150 × 4.6 mm ×5 µm, column oven temperature 40°C, flow rate 1.5 mL/min, Injection volume 10 µL with run time 12.0 minutes at 254 nm using Acetonitrile and buffer as mobile phase in gradient mode. Results: The developed method meets all system suitability parameters and found specific to determine the drug in the presence of Excipient as no interference was observed at the Retention time (Rt) of analyte. Conclusion: There was no physical and chemical incompatibility observed with Drug-Excipient and did not observe significant increase in the related substances.

Determination of astilbin in dietary supplements containing Smilax glabra using high-performance liquid chromatography

Smilax glabra rhizoma (SGR) has been used in traditional medicine remedies for the treatment of joint pain and inflammation, and recently, has been presented in dietary supplements for supporting arthritis and gout treatment. In the 5th Vietnamese Pharmacopoeia, astilbin was chosen as a chemical marker for the quality control of Smilax glabra as herbal medicine. A high performance liquid chromatographic (HPLC) method was developed for the qualitative and quantitative determination of astilbin in dietary supplements containing Smilax glabra. Ultrasonic extraction with 60% methanol was used for astilbin extraction from herbal products. HPLC analysis was performed with a C18 column and a mobile phase consisting of methanol and water in gradient mode, with UV detection at 291 nm. The method was validated according to AOAC International’s requirements with high specificity and precision.

A new RP-HPLC method as an auxiliary tool for optimization of sample preparation procedures for tracing of PPCPs of different hydrophilicities

Recently, pharmaceutical and personal care products (PPCPs) have received considerable attention because of their increasing use. Analysis of PPCPs presents a significant analytical challenge, with high-performance liquid chromatography (HPLC) in reversed-phase mode, as the most widely used analytical technique. To facilitate the optimization of the procedures that are applied in the early stages of sample preparation, a simple and fast HPLC method is proposed in this work for the separation of some PPCPs with a wide range of hydrophilicity. Two columns were evaluated (Atlantis dC18 and Discovery HS F5); as for mobile phases: a formate buffer (40 mmol L−1, pH 4) and methanol were tested in a gradient mode. The fluorinated column allowed better separation in a shorter time and better resolution for all analytes (Rs > 1). The proposed method delivered good performance for the tracing of PPCPs and is a suitable alternative to traditional C18-based HPLC methods.

Calculating the linear critical gradient for the ion-temperature-gradient mode in magnetically confined plasmas

A first-principles method to calculate the critical temperature gradient for the onset of the ion-temperature-gradient mode (ITG) in linear gyrokinetics is presented. We find that conventional notions of the connection length previously invoked in tokamak research should be revised and replaced by a generalized correlation length to explain this onset in stellarators. Simple numerical experiments and gyrokinetic theory show that localized ‘spikes’ in shear, a hallmark of stellarator geometry, are generally insufficient to constrain the parallel correlation length of the mode. ITG modes that localize within bad drift curvature wells that have a critical gradient set by peak drift curvature are also observed. A case study of near-helical stellarators of increasing field period demonstrates that the critical gradient can indeed be controlled by manipulating the magnetic geometry, but underscores the need for a general framework to evaluate the critical gradient. We conclude that average curvature and global shear set the correlation length of resonant ITG modes near the absolute critical gradient, the physics of which is included through direct solution of the gyrokinetic equation. Our method, which handles the general geometry and is more efficient than conventional gyrokinetic solvers, could be applied to future studies of stellarator ITG turbulence optimization.