Development of a New LC-MS/MS Screening Method for Detection of 120 NPS and 43 Drugs in Blood

In the last few years, liquid chromatography coupled with mass spectrometry (LC/MS) has been increasingly used for screening purposes in forensic toxicology. These techniques have the advantages of low time/resource-consuming and high versatility and have been applied in numerous new multi-analytes methods. The new psychoactive substance (NPS) phenomenon provided a great impulse to this wide-range approach, but it is also important to keep the attention on “classical” psychoactive substances, such as benzodiazepines (BDZ). In this paper, a fully validated screening method in blood for the simultaneous detection of 163 substances (120 NPS and 43 other drugs) by a dynamic multiple reaction monitoring analysis through LC-MS/MS is described. The method consists of a deproteinization of 200 µL of blood with acetonitrile. The LC separation is achieved with a 100 mm long C18 column in 35 min. The method was very sensitive, with limits of quantification from 0.02 to 1.5 ng/mL. Matrix effects did not negatively affect the analytical sensitivity. This method proved to be reliable and was successfully applied to our routinary analytical activity in several forensic caseworks, allowing the identification and quantification of many BDZs and 3,4-methylenedioxypyrovalerone (MDPV).

Chronopharmacology in Therapeutic Drug Monitoring—Dependencies between the Rhythmics of Pharmacokinetic Processes and Drug Concentration in Blood

The objective of the optimization of pharmacotherapy compliant with the basic rules of clinical pharmacology is its maximum individualization, ensuring paramount effectiveness and security of the patient’s therapy. Thus, multiple factors that are decisive in terms of uniqueness of treatment of the given patient must be taken into consideration, including, but not limited to, the patient’s age, sex, concomitant diseases, special physiological conditions (e.g., pregnancy, lactation, extreme age groups), polypharmacotherapy and polypragmasia (particularly related to increased risk of drug interactions), and patient’s phenotypic response to the administered drug with possible genotyping. Conducting therapy while monitoring the concentration of certain drugs in blood (Therapeutic Drug Monitoring; TDM procedure) is also one of the factors enabling treatment individualization. Furthermore, another material, and yet still a marginalized pharmacotherapeutic factor, is chronopharmacology, which indirectly determines the values of drug concentrations evaluated in the TDM procedure. This paper is a brief overview of chronopharmacology, especially chronopharmacokinetics, and its connection with the clinical interpretation of the meaning of the drug concentrations determined in the TDM procedure.

A Review on Floating and Mucoadhesive Drug Delivery System

The main goal of just about every drug delivery system is to supply preferred concentrations of drugs in blood and other body fluids, which would be clinically useful and non-hazardous for a long period of time. The Floating and Mucoadhesive both are coming under the novel drug delivery system in which they considered as predominantly more effective as compared to alternative drug delivery system because this formulation having direct contact with a biological system. The latest developments of FDDS and mucoadhesive including the biological and methodology factors that affect Gastrointestinal residence time, the main mucosal system which is explained, the structure of the main formulation described, approaches to develop single-unit and various different-unit floating and mucoadhesive systems, advantages, and one's categorization and development, in which the material used for floating mucoadhesive formulation preparation and other material which are shown on the rationale of their use in this formulation, aspects characterization are enlisted like Thickness and Diameter Testing, Bioadhesion Test, Drug Content Uniformity Test, X Rays Studies Water Uptake Studies, etc. This review also describes the studies to assess the effectiveness and implementation of floating systems, and applications of mucoadhesive systems.

Pharmacologically active vanadium species: distribution in biological media and interaction with molecular targets

: Biospeciation of some of the most studied vanadium (symbol V) complexes with biological or medicinal activity is discussed in this review in order to emphasize the importance of the distribution of V species in biological media. The exact knowledge of the chemical species present in blood or cells may provide essential information about the biological effect of V potential drugs. In blood serum vanadium species can interact with low (citrate, lactate, oxalate, amino acids, etc., indicated with bL) and high molecular mass (proteins like transferrin, albumin, immunoglobulins, etc.) components, while the interaction with red blood cells can interfere with the transport of these drugs towards the target cells. The interaction with bLs and proteins is discussed through the analysis of instrumental and computational data. The fate of the active V species, when these are in the real serum samples and when reach and cross cell membranes, is also discussed. The differences in the V complexes selected in this review (donor atoms, stability, coordination geometry, electric charge, hydro- lipophilicity balance, substituents and redox properties) cover all the possible mode of interaction withbLs and proteins, allowing for the biodistribution of the studied compounds to be predicted. This approach could be applied to newly synthesized potential V drugs.

The Protein-Binding Behavior of Platinum Anticancer Drugs in Blood Revealed by Mass Spectrometry

Cisplatin and its analogues are widely used as chemotherapeutic agents in clinical practice. After being intravenously administrated, a substantial amount of platinum will bind with proteins in the blood. This binding is vital for the transport, distribution, and metabolism of drugs; however, toxicity can also occur from the irreversible binding between biologically active proteins and platinum drugs. Therefore, it is very important to study the protein-binding behavior of platinum drugs in blood. This review summarizes mass spectrometry-based strategies to identify and quantitate the proteins binding with platinum anticancer drugs in blood, such as offline high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC–ICP-MS) combined with electrospray ionization mass spectrometry (ESI-MS/MS) and multidimensional LC–ESI-MS/MS. The identification of in vivo targets in blood cannot be accomplished without first studying the protein-binding behavior of platinum drugs in vitro; therefore, relevant studies are also summarized. This knowledge will further our understanding of the pharmacokinetics and toxicity of platinum anticancer drugs, and it will be beneficial for the rational design of metal-based anticancer drugs.

The most significant reasons for the failure of treatment of patients with newly diagnosed pulmonary tuberculosis and possible solutions

ABSTRACT. The paper summarizes the results of studies regarding the most significant causes of ineffective treatment of patients with newly diagnosed pulmonary tuberculosis. It is proven that the effectiveness of treatment depends from the maximum concentration of antituberculosis drugs in blood serum, tissues and foci of affected lungs, depending on the method of administration of drugs and the presence of concomitant pathology from hepatobiliary and gastrointestinal system tract. Recommendations are given regarding the prevention of ineffective treatment of patients with pulmonary tuberculosis by improving diagnosis and developing new treatment regimens.