Background and Objective In this study, turbo-ion spray as an interface of tandem mass spectrometry (MS/MS) was performed for sensitive and accurate quantification of chlorpromazine, haloperidol, levomepromazine, olanzapine, risperidone, and sulpiride in plasma samples. Methods Separation was performed by gradient reversed phase high-performance liquid chromatography using a mobile phase containing ammonium formiate 2 mM, pH 2.7, and acetonitrile flowing through a Restek PFP Propyl C18 analytical column (50 mm×2.1 mm i.d.) with particle size of 5 µm, at a flow rate of 800 µL/min. Positive ion fragments were detected in multiple reaction monitoring (MRM) mode. Sample preparation was achieved by solid phase extraction (SPE) (Oasis HLB). Results Mean extraction recoveries ranged from 82.75% to 100.96%. The standard calibration curves showed an excellent linearity, covering subtherapeutic, therapeutic, and toxic ranges. Intraday and interday validation using quality control (QC) samples were performed. The inaccuracy and imprecision were below 12% at all concentration levels. The limits of detection (LOD) and quantification (LOQ) for all analytes were under therapeutic ranges for all tested analytes. Thus, the proposed method was sensitive enough for the detection and determination of subtherapeutic levels of these antipsychotics in plasma samples. No interference of endogenous or exogenous molecules was observed and no carryover effects were recorded. Conclusion According to the results, the proposed method is simple, specific, linear, accurate, and precise and can be applied for antipsychotic analysis in clinical routine. This method was applied for the determination of the tested antipsychotics in plasma samples taken from 71 individuals.

Therapeutic enzymes have a broad variety of specific uses and clinical applications, particularly as antineoplasic agents, wound debridement therapeutics, and anti-inflammatory drugs, etc. These enzymes can elicit immune response, contributing allergic reactions. Newer drugs with improved stability and less antigenicity have been developed. Covalent modification of enzymes is used to circumvent this immunogenicity. Advancements in drug delivery have revolutionized enzyme therapy. Microencapsulation and artificial liposomal entrapment are some of the techniques used to increment the stability and half-life of enzyme drugs. Several enzymes are now used as prodrug that metabolizes inactive substances into active metabolites through bioactivation process. This approach comprises a suit of techniques that allow activation of drugs locally and at the site of action. This chapter gives an outline of clinical uses of therapeutic enzymes used in non-deficiency diseases. Developments of these enzymes are reviewed with a particular focus on bioengineering applied to the native proteins.

Introduction The atherosclerosis process is highly accelerated in patients with chronic kidney disease (CKD). Oxidative stress is considered as one of the pro-atherogenic factors involved in accelerating the atherosclerosis process of the carotid artery. The aim of the present study was to determine the relationship between oxidative stress markers and the progression of carotid atherosclerosis in CKD patients. Material and methods The study was conducted on 162 patients with CKD and 40 controls, and the disease stage was scored between 2 and 5D. Blood samples were taken and advanced oxidative protein product, myeloperoxidases, malondialdehyde, nitric oxide, glutathione, and oxidised low-density lipoprotein were measured. Furthermore, we studied the correlations between these biomarkers and clinical and para-clinical cardiovascular complications. Results The average age of patients was 56.5 years. The oxidative stress markers average ± SD levels in CKD groups compared to the control were as follows: advanced oxidation protein product (61.89 ±1.4 vs. 26.65 ±1.05 µmol/l), myeloperoxidase (59.89 ±1.98 vs. 38.45 ±1.98 UI/ml), malondialdehyde (6.1 ±0.12 vs. 3.26 ±0.03 µmol/l), nitric oxide (65.82 ±1.06 vs. 52.19 ±2.1 µmol/l), glutathione (52.21 ±1.3 vs. 89.4 ±2.6 IU/ml), and oxLDL (15.57 ±1.07 vs. 1.72 ±0.82 µmol/l). While the glutathione level decreased significantly in advanced CKD stage ( p < 0.05), the concentrations of all the other biomarkers increased significantly in accordance with CKD score ( p < 0.05). Conclusions Cardiovascular diseases, mainly atherosclerosis, can be diagnosed indirectly by measuring oxidative stress markers. Furthermore, theses markers can be used to predict the progression of CKD, for better management of the disease.

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