Analysis Of Pharmaceutical Compounds Research Articles

Fabric phase sorptive extraction: A sustainable approach in analysis of pharmaceutical product

As the pharmaceutical industry continues to evolve, there is an increasing demand for sustainable and efficient analytical techniques in the analysis of pharmaceutical products. This manuscript explores the application of Fabric Phase Sorptive Extraction (FPSE) as a novel and sustainable approach for the extraction and analysis of pharmaceutical compounds. FPSE, a recent advancement in sample preparation, offers a greener alternative by utilizing a fabric-like sorbent material. The environmentally friendly nature of FPSE, with reduced solvent consumption and waste generation, aligns with the principles of green analytical chemistry. Case studies involving the analysis of various pharmaceutical products showcase the versatility and applicability of FPSE in different matrices.

Density Functional Theory Calculation of Molecular Descriptors for Simple Coumarins in Gas and Different Solvents

The primary aim of this study is to show the importance of molecular structure analysis of pharmaceutical active coumarins compounds using quantum chemistry methods based on density functional theory. To explore the theoretical calculations for global descriptors, the standard Gaussian 09W program was used for coumarins compounds. The full geometry optimization was carried out by the B3LYP/6-311G level of theory. The octanol-water and air-water partition coefficients were also estimated using functional density theory. The order of the HOMO-LUMO energy gap for studied coumarins in the gas phase is umbelliferone (UBA) < (herniarin) HNR ~ (crenulatin) CNT < (scopoletin) SCT < (scoparone) SCO < (isoscopoletin) IST < (4-methylesculetin) MST < (umbelliferone-2- carboxylic acid) UCA < (isofraxidin) IFD < (fraxetin) FXT < (aesculetine) ACT < (dapnetine) DPT. Therefore, UBA molecule in gas phase is less stable. Compared to the measured index of electrophilicity (DE). The MST molecule is stronger, more reactive, nucleophile electrophile at the gas phase and in solvents. In all solvent phases, CNT and UCA molecules have lower values, which mean they are strong nucleophiles. From the log P values of ACT and MST coumarins are in between 1.35-1.8, so ACT and MST coumarins use oral and intestinal absorptions.

An atmospheric pressure ionization source using a high voltage target compared to electrospray ionization for the LC/MS analysis of pharmaceutical compounds

The type and design of an ionization source can have a significant influence on the performances of a bioanalytical method. It is, therefore, of high interest to evaluate the performances of newly introduced sources to highlight their benefits and limitations in comparison to other well established sources. In this paper, liquid chromatography – mass spectrometry (LC/MS) performances of a new atmospheric pressure ionization (API) source, commercialized as UniSpray, is evaluated. The dynamic range of 24 pharmaceutical and biological compounds is compared between the new API source and electrospray ionization (ESI) for 3 different mobile phase conditions. Matrix effects are also compared with ESI on a refined selection of 19 pharmaceutical and biological compounds in 4 matrices commonly encountered in bioanalysis.A slightly better dynamic range towards lower concentrations was often observed with the new API source. Matrix effects were quite similar between the two sources with a small, but statistically significant, lower percentage of matrix effects observed for the new API source in plasma and bile in the positive ion mode, and bile in negative ion mode for ESI. Finally, the sensitivity of late eluting compounds could be improved on the new API source by post-column addition of water.

Atmospheric Pressure Ionization Using a High Voltage Target Compared to Electrospray Ionization.

A new atmospheric pressure ionization (API) source, viz. UniSpray, was evaluated for mass spectrometry (MS) analysis of pharmaceutical compounds by head-to-head comparison with electrospray ionization (ESI) on the same high-resolution MS system. The atmospheric pressure ionization source is composed of a grounded nebulizer spraying onto a high voltage, cylindrical stainless steel target. Molecules are ionized in a similar fashion to electrospray ionization, predominantly producing protonated or deprotonated species. Adduct formation (e.g., proton and sodium adducts) and in-source fragmentation is shown to be almost identical between the two sources. The performance of the new API source was compared with electrospray by infusion of a mix of 22 pharmaceutical compounds with a wide variety of functional groups and physico-chemical properties (molecular weight, logP, and pKa) in more than 100 different conditions (mobile phase strength, solvents, pH, and flow rate). The new API source shows an intensity gain of a factor 2.2 compared with ESI considering all conditions on all compounds tested. Finally, some hypotheses on the ionization mechanism, similarities, and differences with ESI, are discussed. Graphical Abstract ᅟ.

Quantitative analysis of drugs in biological matrices by HPLC hyphenated to fluorescence detection.

An overview of the state-of-the art in HPLC coupled with fluorescence detection is presented. Over the last 20 years, the increasing number of methodological papers on this topic (4082 between 1994 and 2004 and 7725 between 2004 and 2014) is testament to its utility in bioanalytical applications. Compared with conventional UV absorbance detection used in HPLC, fluorescence detection can greatly enhance the sensitivity leading to limits of detection similar to those obtained with mass spectrometry, offering researchers a sensitive, robust and relatively inexpensive instrumental method. This work will focus on the analysis of pharmaceutical compounds in different biological matrices, either naturally fluorescent or derivatized with a fluorescent agent, and some of them chiral. Therapeutic applications, sample preparation and derivatization, sensitivity for each example are described.

Validation of a method for the determination of AMG 579 in cerebrospinal fluid with a focus on sample collection procedures for clinical trials

Analysis of pharmaceutical compounds in cerebrospinal fluid (CSF) may present challenges due to the combination of the low protein content in this matrix and relatively low drug concentrations, often corresponding to free drug concentrations in plasma, typically found in CSF. A 30% loss of AMG 579 was observed during preparation of quality control samples and further investigation determined that this loss was likely due to binding to collection tubes. This observation also highlighted the possibility of additional losses of AMG 579 that could occur during collection of clinical samples, such as binding to catheters used in the collection of CSF.Loss of AMG 579 in QC samples was reduced from 30% to 5% when the volume of CSF stored in 1.5mL vials was increased from 0.06mL to 1mL. Modest but unavoidable losses of about 20% of AMG 579 were also found following perfusion through both silicone and polypropylene (Pharmed® BPT) collection catheters. Silicone tubing was used for CSF collection based on clinical site preference. An LC–MS/MS method was validated to quantify AMG 579 in human CSF to support clinical testing. The original range of the assay was 1–1000ng/mL but the LLOQ was subsequently lowered to 0.1ng/mL to better meet project requirements. Interday bias (% RE) and precision (% CV) were −4.2% and 12.3% at the LLOQ, and less than ±0.9% and 8.3% for higher concentrations, respectively. The compound was stable in human CSF for at least 5h at room temperature, 55 days at −70°C (−60 to −80°C range), and through three freeze–thaw cycles.Careful selection of assay conditions and materials minimized losses of the compound during sample collection and storage. While these losses could not be entirely eliminated, practical sample collection and storage conditions were established to allow for analysis of AMG 579 in human clinical trials.

Statistical evaluation of the influence of soil properties on recoveries and matrix effects during the analysis of pharmaceutical compounds and steroids by quick, easy, cheap, effective, rugged and safe extraction followed by liquid chromatography–tandem mass spectrometry

Numerous chemical products are dispersed in our environment. Many of them are recognized as harmful to humans and the ecosystem. Among these harmful substances are antibiotics and steroid hormones. Currently, very few data are available on the presence and fate of these substances in the environment, in particular for solid matrices, mainly due to a lack of analytical methodologies. Indeed, soil is a very complex matrix, and the nature and composition of the soil has a significant impact on the extraction efficiency and the sensitivity of the method. For this reason a statistical approach was performed to study the influence of soil parameters (clay, silt, sand and organic carbon percentages and cation exchange capacity (CEC)) on recoveries and matrix effects of various pharmaceuticals and steroids. Thus, an analysis of covariance (ANCOVA) was performed when several substances were analyzed simultaneously, whereas a Pearson correlation was used to study the compounds individually. To the best of our knowledge, this study is the first time such an experiment was performed. The results showed that clay and organic carbon percentages as well as the CEC have an impact on the recoveries of most of the target substances, the variables being anti-correlated. This result suggests that the compounds are trapped in soils with high levels of clay and organic carbon and a high CEC. For the matrix effects, it was shown that the organic carbon content has a significant effect on steroid hormones and penicillin G matrix effects (positive correlation). Finally, interaction effects (first order) were evaluated. This latter point corresponds to the crossed effects that occur between explanatory variables (soil parameters). Indeed, the value taken by an explanatory variable can have an influence on the effect that another explanatory variable has on a dependent variable. For instance, it was shown that some parameters (silt, sand) have an impact on the effect that clay content has on recoveries. Besides, CEC and silt affect the influence that organic carbon percentage has on matrix effect. This original approach provides a better understanding of the complex interactions that occur in soil and could be useful to understand and predict the performance of an analytical method.

Fast RPLC analysis of pharmaceutical compounds at intermediate temperatures by using a conventional instrument

Recent developments in HPLC methods have focused on various strategies in order to increase the speed of analysis. One area of impressive growing is column technology. Today, analytical methods that propose the use of short columns packed with sub-2 μm particles installed in ultra high-pressure LC instruments are not uncommon. Another strategy consisted of heating thermally resistant columns to temperatures well above of 100°C in order to reduce eluent viscosities and, therefore, column backpressure. We discuss experimental conditions for achieving high-throughput analysis using standard instruments with a few simple modifications. The chromatographic performance of two particulated and a silica-based monolithic column operated at moderate temperatures and flow rates are compared. The monolithic column proved to be stable over several thousands column volumes at 60°C. More important, its resistance to mass transfer at this temperature was significantly reduced. Very fast separations of two different mixtures of pharmaceutical compounds, anti-inflammatory drugs and β-blockers, were achieved with the three columns at 60°C by using ACN/buffer at 5 mL/min. Excellent peak shapes of basic solutes and quite reasonable resolutions were achieved in very short analysis times with columns operated at temperatures moderately higher than the usual room temperature.

Analysis of Pharmaceutical Compounds from Glass, Fabric, Steel, and Wood Surfaces at Atmospheric Pressure Using Spatially Resolved, Nonresonant Femtosecond Laser Vaporization Electrospray Mass Spectrometry

Laser electrospray mass spectrometry (LEMS) is demonstrated for pharmaceutical samples at atmospheric pressure. A nonresonant, femtosecond duration laser pulse vaporizes native samples at atmospheric pressure into an electrospray plume for ionization with subsequent transfer into a time-of-flight mass spectrometer. The active ingredients in pharmaceutical tablets were detected in the presence of binders and fillers in intact formulations using LEMS. Mass spectra were also obtained for microgram amounts of the pharmaceutical compounds loratadine, oxycodone, and atenolol deposited on glass, wood, steel, and polyester fabric. The neutral capture efficiency by the electrospray plume for nonresonant laser vaporization of oxycodone and atenolol desorbed from steel is 2.4% +/- 1.5% and 0.25% +/- 0.18%, respectively. LEMS imaging of the spatial distribution of an oxycodone spot on a metal slide with resolution of 250 mum is also presented.

Utilizing ion mobility spectrometry combined with mass spectrometry for analysis of pharmaceutical compounds

Utilizing ion mobility spectrometry combined with mass spectrometry for analysis of pharmaceutical compounds

Enhanced Performance Test Mix for High-Throughput LC/MS Analysis of Pharmaceutical Compounds

LC/MS is being used for the routine analysis of small molecules in both the discovery and development stages within the pharmaceutical industry. In drug discovery, LC/MS is relied upon to confirm the identity and assess the purity of chemical entities. To ensure the quality of LC/MS analysis, it is important that the LC/MS system is operating within defined performance criteria. Performance monitoring of the system with a standard compound mix offers many advantages over other alternatives, since it monitors the LC/MS system as an integrated unit under the same working conditions as those used for the analysis of samples. It is also a convenient approach, because the test mix can be injected as part of the automated sequence. Use of a test mix for similar purposes has been described previously (Tang, L.; Fitch, W. L.; Alexander, M. S.; Dolan, J. W. Anal. Chem. 2000, 72, 5211-5218). To monitor the performance of ArQule's LC/MS operation (with UV and ELS detection) in greater detail, a set of eight compounds was selected from a collection of 137 commercially available "druglike" compounds. The compounds are generally stable and compliant with the rule-of-five criteria. This enhanced mix has a balanced selection of pKa values and covers the typical range of hydrophobicity and molecular masses of pharmaceutical compounds. Moreover, the selected compounds can generally be ionized using ESI and APCI modes with positive and negative polarity. The test mix can be used under formic acid or ammonium hydroxide conditions and with methanol or acetonitrile as an organic modifier. Performance monitoring with the enhanced mix is demonstrated with respect to ionization and mass measurement, as well as changes in gradient profile, flow rate, buffer pH, and ionic strength.

Effect of temperature on the retention of ionizable compounds in reversed-phase liquid chromatography: Application to method development

The analysis of pharmaceutical compounds is often a difficult challenge which requires mathematical tools to improve the quality of the separation method. This work is an attempt to rationalize the anomalous variation of the logarithm of the retention factor with temperature in case of ionizable compounds. The effect of temperature on ionizable compounds was studied within a large range of temperature, ranging from 30 to 130 °C. The determination of the so-called chromatographic p K a and the study of its variation with temperature allow to explain why the forms of the van’t Hoff curves are so different depending on the type of solute, the type of buffer and the type of the mobile phase. A retention model along with a computation procedure is proposed to optimize both temperature and mobile phase composition and to provide good and robust conditions as shown by illustrative examples.

Comparison of dodecoxycarbonylvaline microemulsion, solvent-modified micellar and micellar pseudostationary phases for the chiral analysis of pharmaceutical compounds

Comparison of dodecoxycarbonylvaline microemulsion, solvent-modified micellar and micellar pseudostationary phases for the chiral analysis of pharmaceutical compounds

Practical Applications of Monolithic Columns to Pharmaceutical Process Development

High performance liquid chromatography (HPLC) is among the most widely used analytical techniques in the process development of drug substances. With the goal of reducing analysis time, there has been considerable focus on high‐speed HPLC separations. Recently, commercially available monolithic columns have proven to be one of the most promising developments in the area of fast chromatographic separations. In this work, pressure drop, column efficiency, and retention behavior of monolithic columns (Chromolith type) were evaluated and compared with those of conventional columns packed with porous stationary‐phase particles. It was demonstrated that high‐speed HPLC separations could be achieved with monolithic columns at acceptable pressure drops without significantly compromising column efficiency. The applications of monolithic columns in pharmaceutical process development, such as reaction monitoring, column fraction screening, and analysis of mother liquors and unstable analytes, are described with respect to the quality of separations, as well as, enhanced throughput and speed of analysis. It is concluded that the use of monolithic columns offers a significant advancement over currently available techniques in the high‐speed and high‐throughput analysis of pharmaceutical compounds. Some practical aspects in utilizing monolithic columns for fast separations are also discussed.

Direct analysis of nine pharmaceuticals in culture media by use of cartridge separation with electrospray mass spectrometric detection.

A 2-cm cartridge has been used for separation before electrospray mass spectrometric analysis of pharmaceutical compounds in cell culture media, alleviating the need for sample extraction and desalting procedures. Nine representative pharmaceuticals listed in the biopharmaceutical classification system (BCS) were chosen as the candidate compounds and Hank's balanced salt solution with Hepes buffer (HBSS-Hepes buffer) was used as the cell-culture medium in an effort to study permeability of chemicals through cell monolayers. Effects of several conditions, e.g. pH and buffer concentration in the mobile phase, flow rate, and temperature on separation efficiency were examined. The nine pharmaceuticals were separated within 2 min by use of a 2-cm C(8) cartridge. Relative standard deviations (RSD) from repeated analysis within the same day or over five days were 0.03-0.2% for retention times and 0.6-5.3% for peak areas; antipyrine was used as internal standard. Calibration curves based on peak-area measurements were linear over the range 0.1-20 micro mol L(-1). The HBSS-Hepes buffer did not interfere with separation and detection; identical separation and peak intensity were obtained when the samples were separately prepared in distilled water or in the culture medium.

Direct analysis of crude plasma samples by turbulent flow chromatography/tandem mass spectrometry

Turbulent flow chromatography coupled to tandem mass spectrometry (TFC-MS-MS) has recently emerged as a potentially fast, sensitive and specific technique for the direct analysis of pharmaceutical compounds from crude plasma. TFC-MS-MS removes the need for time-consuming sample preparation procedures such as solid-phase extraction (SPE) or liquid-liquid extraction (LLE). A relatively high flow rate combined with the use, of an HPLC column with large porous particles allows the on-line clean up and quantification of compounds in plasma samples. Until, now, the amount of plasma directly injected into TFC systems has rarely exceeded 30 μL in order to prevent rapid column degradation. Increasing the injection volume also induces high carry-over levels, particularly for drugs with basic and/or lipophilic properties. This paper describes the first genetic TFC-MS-MS method developed in a 96-well format, which allows the direct injection of 200 μL of 1∶1 diluted plasma (equivalent to 100 μL neat plasma). An average, of 390 injections was carried out with each extraction column. More than 2000 dog plasma samples were injected into the system without any sign of carryover. The method was fully validated over a 5–500 ng mL−1 range for three basic compounds: doxazosin, CP122,288 and dofetilide. The imprecision was 1.2 to 8.3% for doxazosin, 1.5 to 4% for CP122,288 and 1.6 to 9.2% for dofetilide. The inaccuracy ranged from 6% to 7.9%. This generic methodology was then used to assay two structurally unrelated development compounds, showing that the method accuracy and sensitivity were adequate for the early pharmacokinetic (PK) studies in animals.

Selectivity manipulation using nonaqueous capillary electrophoresis. Application to tropane alkaloids and amphetamine derivatives.

Non-aqueous capillary electrophoresis was investigated for its potential in the analysis of pharmaceutical compounds, namely tropane alkaloids and amphetamine derivatives. The separation of these drugs was compared in aqueous and organic media such as methanol and/or acetonitrile. Selectivity, migration times and efficiency were critically affected by the composition of the methanol/acetonitrile mixture, as well as by the nature and the concentration of the electrolyte. In particular, the migration orders of two positional isomers, littorine and hyoscyamine, were inverted in the presence of trifluoroacetic acid in the nonaqueous medium. The same behavior was observed for amphetamine-methamphetamine and for two methylenedioxyamphetamine derivatives.

Capillary electrophoresis in pharmaceutical analysis.

Capillary electrophoresis (CE) is a separation technique particularly suited to the analysis of pharmaceutical compounds. This review offers a detailed discussion of the four common modes of detection coupled to CE-UV absorption, fluorescence, electrochemical, and mass spectrometry-and gives examples of the use of these methods in pharmaceutical analyses. Sample preparation and pretreatment techniques used for CE separations are described, as well as methods of preconcentration including hydrophobic retention, affinity concentration, sample stacking, and isotachophoresis. The use of affinity CE, chiral CE, and capillary gel electrophoresis for analysis of pharmaceuticals is covered in detail, and recent advances in capillary electrochromatography and CE on a chip are also discussed.

The analysis of pharmaceutical compounds using electrochromatography

Electrochromatography couples the very high efficiencies associated with capillary zone electrophoresis, with reversed-phase liquid chromatography (RPLC). Therefore, electrochromatography couples the differences in electrophoretic mobilities of related species, with the modification of selectivities that are available to users of RPLC through variation of the stationary and mobile phases. Electrochromatography uses an electric field to drive the mobile phase through a packed capillary, and because the resulting flow profile is plug-like, very high efficiencies are achieved. Also, the linear flow through a packed capillary in electrochromatography is independent of the particle diameter, and since the driving force (electroosmosis) produces no hydrostatic pressure, it is possible to use very small diameter particles and consequently generate large theoretical plate values often>300,000 plates per metre with reduced plate heights<1. The capabilities of electrochromatography are demontrated by means of the analysis of several drug compounds.

Knowledge representation for the selection of methods in analytical chemistry

Abstract Expert systems are gaining rapidly in importance in several areas of science, and in chemistry in particular. One of the most important factors that determines the success of an expert system is the representation of the knowledge. To understand better the suitability of the different knowledge representation techniques for the selection of methods in analytical chemistry, a test knowledge base was developed for the high-performance liquid chromatographic analysis of pharmaceutical compounds. This knowledge base has been used to study which features of knowledge representation are necessary to describe analytical chemical knowledge in a natural and efficient way. It is concluded that no single representation method is optimal. A combination of production rules and frame structures seems to be much more suitable. The possibility of consulting external databases and programs is also a very important aspect.