Biomedical Chromatography

Suresh, P.S.; Srinivas, Nuggehally R.; Mullangi, Ramesh

doi: 10.1002/bmc.4034pmid: 28636139

Prostate cancer is the most common cancer and one of the leading causes of cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first‐generation nonsteroidal anti‐androgens (NSAAs), namely flutamide, nilutamide, bicalutamide and topilutamide. Most prostate cancer patients who are initially responsive develop the most aggressive form of disease called castration‐resistant prostate cancer. Second‐generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat castration‐resistant prostate cancer. The objective of this work was to review the literature on the bioanalytical methods for the quantification of first‐ and second‐generation NSAA inhibitors in clinical (human plasma) and preclinical (mouse plasma, rat plasma, urine and tissue homogenates etc.) studies along with relevant case studies for some chosen drugs. Based on the review, it was concluded that the published methodologies using either HPLC or LC–MS/MS are well suited for the quantification of NSAA inhibitors in various biological fluids to delineate pharmacokinetic data.

Bartlett, Michael G.

doi: 10.1002/bmc.4152pmid: 29235138

Szeitz, András; Bandiera, Stelvio M.

doi: 10.1002/bmc.4135pmid: 29135035

Serotonin, also known as 5‐hydroxytryptamine, is an important signaling molecule in the central and peripheral nervous systems of humans. Acting through several receptor types, it helps regulate the normal functioning of the gastrointestinal tract, cardiovascular system and brain. Serotonin signaling has also been implicated in the etiology of several diseases, including depression, anxiety disorders, hypertension and irritable bowel syndrome. The present review focuses on the chemical analysis of serotonin in biological fluids and biomatrices and traces the development and application of early methods based on UV absorbance or fluorescence to more widely used current methods such as high‐performance liquid chromatography coupled to mass spectrometry. A brief summary of the biochemistry, metabolism and physiological roles of serotonin is also presented.

Farha, Waziha; Abd El‐Aty, A. M.; Rahman, Md. Musfiqur; Jeong, Ji Hoon; Shin, Ho‐Chul; Wang, Jing; Shin, Sung Shik; Shim, Jae‐Han

doi: 10.1002/bmc.4134pmid: 29134675

The category of ‘leafy vegetables’ comprises a wide range of plants, including cabbage, lettuce, leeks, spinach, Swiss chard and kale, and it forms a significant component of the human diet. Typically, leafy vegetables are low in calories and fat, are great sources of vitamins, protein, dietary fibre and minerals (including iron, calcium, and nitrates), and are rich in phytochemicals. To counter the impact of pests on vegetables, a broad variety of pesticides are used. Because of their large surface areas, leafy vegetables are expected to have high residual pesticide levels. As such, a sound analytical approach is needed to detect and quantify residue levels that are equal to or lower than the maximum residue limits, thus rendering the products safe for consumption. Overall, leafy vegetables consumed raw (after a tap water wash only), boiled or steamed contribute 2% of total vegetable consumption globally, and they might have a comparatively greater influence on health than cereal ingestion. Consequently, in this review paper, we highlight the importance of leafy vegetables, the pesticides that are commonly used on them and various analytical techniques, including sample preparation, extraction, clean‐up and final detection. The effects on dissipation patterns, pre‐harvest residue limits and safety/risks imposed by various pesticides are also reviewed and discussed. In conclusion, environmentally friendly extraction methods coupled with high‐throughput techniques with greater reproducibility and lower uncertainty are needed for quantifying residues in leafy vegetables at very low concentrations. Commercial and household food preparation, such as washing, peeling, blanching and cooking are effective in removing most of the pesticide residues that are loosely attached on vegetables.

Hancu, Gabriel; Cârcu‐Dobrin, Melania; Budău, Monica; Rusu, Aura

doi: 10.1002/bmc.4040pmid: 28670837

Fluoxetine is a widely used antidepressant belonging to the selective serotonin reuptake inhibitor class; it is used in the treatment of major depression, obsessive compulsive, premenstrual dysphoric, panic and post‐traumatic stress disorders. Fluoxetine is an optical active pharmaceutical substance, which is used as a racemate in therapy, but stereospecific interactions associated with the serotonin‐reuptake carrier, for both the parent drug and its active metabolite, norfluoxetine, have been described in the literature. Therefore, the stereoselective analysis of fluoxetine and norfluoxetine is important in order to characterize the pharmacokinetic and pharmacodynamic profile of the analytes. Several chromatographic and electrophoretic methods have been published in the literature for the chiral discrimination of fluoxetine enantiomers from different matrices. The purpose of the current review is to provide a systematic survey of the analytical techniques used for the chiral determination of fluoxetine and norfluoxetine covering a period of ~25 years.

doi: 10.1002/bmc.4070pmid: N/A

No abstract is available for this article.

Göktaş, Eylem Funda; Arıöz, Filiz

doi: 10.1002/bmc.4014pmid: 28555942

Ketamine has a synthetic, sedative, nonbarbiturate and fast‐acting anaesthetic properties and it is commonly used in both humans and veterinary surgery. There are many analytical methods available for the qualitative and quantitative determination of ketamine and its metabolites. We have focused on sample pre‐treatment and chromatographic techniques used since the year 2000 for the determination of ketamine and its metabolites in biological samples. Liquid and gas chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection) have been used in these publications. This review gives information on the implementation of methods for studying ketamine and its metabolites in various research applications. It could be useful in forensic sciences including doping control and also in the therapeutic drug monitoring of ketamine and norketamine in human and animal clinical surgery.

Dash, Ranjeet Prasad; Srinivas, Nuggehally R.; Rais, Rana

doi: 10.1002/bmc.4109pmid: 28990207

Sphingosine 1‐phosphate (S1P1) modulators provide an emerging therapeutic approach for various autoimmune disorders such as multiple sclerosis and psoriasis. Fingolimod is the first approved orally active, selective and potent drug of this class. Other drugs belonging to this class include siponimod, ponesimod, ceralifimod, amiselimod, CS‐0777 and GSK2018682. However, owing to the high protein binding, polarity and zwitter‐ionic nature of the phosphate metabolite of parent drugs, it becomes challenging to optimize the extraction method for this class of compounds. Although, there are individual published bioanalytical methods for the analysis of selected S1P1 modulators to support preclinical and clinical drug development, no extensive review compiling all the bioanalytical methods for the important drugs in the class is available. Thus, we attempted to prepare a comprehensive review on various bioanalytical methods for selected S1P1 modulators which will provide all the relevant bioanalytical information as required by bioanalytical researchers. This review focuses on the various liquid chromatography with tandem mass spectrometry methods that have been used to quantify S1P1 modulators in various biological matrices. Extraction methods included liquid–liquid extraction, solid‐phase extraction and one‐step protein precipitation for extracting the analytes. This review captures key information regarding sample processing options and chromatographic/detection conditions.

El Zahar, N. M.; Magdy, N.; El‐Kosasy, A. M.; Bartlett, Michael G.

doi: 10.1002/bmc.4088pmid: 28869310

Phosphorothioate (PS) oligonucleotides are a rapidly rising class of drugs with significant therapeutic applications. However, owing to their complex structure and multistep synthesis and purification processes, generation of low‐level impurities and degradation products are common. Therefore, they require significant investment in quality control and impurity identification. This requires the development of advanced methods for analysis, characterization and quantitation. In addition, the presence of the PS linkage leads to the formation of chiral centers which can affect their biological properties and therapeutic efficiency. In this review, the different types of oligonucleotide impurities and degradation products, with an emphasis on their origin, mechanism of formation and methods to reduce, prevent or even eliminate their production, will be extensively discussed. This review will focus mainly on the application of chromatographic techniques to determine these impurities but will also discuss other approaches such as mass spectrometry, capillary electrophoresis and nuclear magnetic resonance spectroscopy. Finally, the chirality and formation of diastereomer mixtures of PS oligonucleotides will be covered as well as approaches used for their characterization and the application for the development of stereochemically‐controlled PS oligonucleotides.

Batra, Sonika; Bhushan, Ravi

doi: 10.1002/bmc.4090pmid: 28905405

Atenolol, a β‐adrenergic receptor antagonist, is a chiral compound used for the treatment of cardiovascular diseases and to treat hypertension, coronary heart disease, arrhythmias, sinus tachycardia and myocardial infarction, where it acts preferentially upon the β‐adrenergic receptors in the heart. It is marketed as a racemate, but only the (S)‐enantiomer of (RS)‐atenolol is responsible for the β‐adrenoceptor blocking activity. Different chromatographic methods have been applied for the separation and determination of enantiomers. In this article a review is presented on liquid chromatographic methods for enantioseparation of (RS)‐atenolol by both direct and indirect approaches involving practical applications of several chiral stationary phases, chiral derivatization reagents and ligand exchange and impregnation methods. These include methods using both HPLC and TLC for separation, determination and bioassay of enantiomers of atenolol. In addition, some aspects of enantioseparation under achiral phases of liquid chromatography have been briefly mentioned as applicable to (RS)‐atenolol. This review provides current available enantioseparation choices not only for (RS)‐atenolol but also for other applicable racemic drugs.