Current Pharmaceutical Analysis - Volume 18, Issue 7, 2022

Background: With the development of monoclonal antibodies (mAbs) from the first generation of mice to the fourth generation of human origin, the efficacy and safety in the treatment of many diseases have been continuously improved. MAbs have been widely used in the treatment of cancer, chronic inflammatory diseases, etc. However, the treatment response of mAbs varies greatly among individuals, and drug exposure may be affected by a variety of physiological and pathological factors, such as combined use of drugs and progression of the disease. Therefore, studies tend to recommend therapeutic drug monitoring and individualized treatment strategies. Objective: In this paper, the commonly used methods of quantification of monoclonal antibodies were reviewed, especially liquid chromatography- mass spectrometry (LC-MS/MS) and enzymelinked immunosorbent assay (ELISA), to provide technical support for therapeutic drug detection and individualize dosing for patients. Conclusion: For patients achieving mAbs treatment, it is necessary to carry out therapeutic drug monitoring and take it as a routine monitoring index. We recommend that for pharmaceutical laboratories in hospitals, establishing an appropriate assay format, such as ELISA and LC-MS/MS is critical to determine drug concentration and antidrug antibody (ADA) for mAbs.

The application of various sophisticated analytical tools and techniques is essential for estimating an active pharmaceutical ingredient present in either biofluids or pharmaceutical dosage forms. Reporting the multiple analytical methods used to quantify esomeprazole magnesium trihydrate, a proton pump inhibitor, is the ultimate goal of this review article. This article deals with a detailed discussion of different reported analytical procedures along with their pros and cons and their relevant criteria for quantifying the drug. Various analytical techniques like UV-Visible spectrophotometry, HPLC, HPTLC, hyphenated techniques, etc., are developed to assess the esomeprazole magnesium trihydrate in bulk materials, different pharmaceutical formulations, and biological matrices. Literature survey confirmed that the hyphenated techniques and chromatographic techniques are the best tools for biological matrices. Spectroscopic methods like UV and visible techniques are widely used for pharmaceutical matrices. All of the reported methods are accurate, precise, costeffective, and sensitive.

Background: Transdermal drug delivery systems (TDS) are widely used to deliver a number of different drug therapeutics. The design delivery can be impacted by excipients and, more broadly, organic solvents. Organic or residual solvents are routinely monitored due to safety concerns. However, there is little information on the mechanical properties and delivery performance of TDS. Objective: The objective of this study was to develop and validate an efficient GC-Headspace method to determine the residual solvents (n-heptane, o-xylene, and ethyl acetate) in transdermal patches. The analytical method was applied to monitor residual solvents in TDS and evaluate the potential effect of the residual solvent levels on the TDS adhesion properties. Methods: An Agilent GC 7890A was integrated with an Agilent headspace analyzer 7697A system and was used for method development, analytical method validation, and the testing phases of the study. For the analysis of residual solvents in TDS, 2cm x 3cm, a TDS sample was placed in a 20 mL Headspace vial containing 2 mL of a DMSO/water (1:1, v/v) solvent mixture, and an external standard (cyclohexane) was extracted by the headspace analyzer. The system suitability test was conducted according to USP <621>, and analytical method validation was conducted according to USP <1225> over 3 days for validation and was also performed during in-study sample analysis. Results: The resolution between the solvents was acceptable (2.5, %RSD = 8.0). Intra- and inter- day accuracy and precision of all quality control standards as well as the spiked standards in the transdermal patches were found to be acceptable with RSD% ≤ 10% and accuracy ≥ 85%, respectively. Linearity was > 0.99 for all analytes. Conclusion: The validated GC-Headspace method was successfully applied to a pilot study for in-house manufactured TDS patches to study the impact of residual solvent concentration on adhesion performance.

Objective: Shenhuang (SH) capsule is a traditional Chinese medicine compound preparation containing rhubarb, coptis, scutellaria, salvia and Pueraria, used for diabetic nephropathy studied by our research group in the early stage. This study aims to develop the method of qualitative identification and content determination of the main active ingredients of SH capsules so as to establish the quality standard. Methods: HPLC method was used to determine the contents of rhein, Pueraria, and tanshinone in SH capsules. The determination method of SH capsules was established through the determination of specificity, regression equation, precision, repeatability, and recovery. The general quality standard of SH capsules was established by measuring water content, disintegration time, and microorganism. The contents of rhein, puerarin, and tanshinone IIA in SH capsules were determined by HPLC. Results: The precision was 1.10–3.00% and the reproducibility and recovery rates were 95.0– 105.7%. The moisture determination, disintegration time, and microorganism examination of SH capsule were all in line with the standard. Conclusion: The stable, feasible, simple, and reliable content determination method was established through the content determination of SH capsules and the general quality standard test.

Background: We systematically characterized an allergic dimer impurity in cefmenoxime hydrochloride raw material by UV, IR, HR-MS, 1D, and 2D NMR for the first time. Methods: The dimer stock solution of cefmenoxime hydrochloride was obtained by the degradation method. The target dimer impurity in the stock solution was separated by preparative RP-HPLC and purified by the freeze-drying method. By comparing the dimer to cefmenoxime hydrochloride, the functional groups corresponding to the characteristic peaks of UV and IR spectra were identified, and the molecular formula and mass fragmentation pattern were determined using HR-MS. Results: Then, based on the full assignment of ¹ H and ¹³ C NMR signals#140; the dimerized position was confirmed and its absolute configuration was identified by 1D and 2D NMR. Conclusion: This study provided a structural basis for the allergic study of dimer impurities in cephalosporin drugs.

Background:Characterization of allergic polymerized impurities in cephalosporins is significant to ensure the safety and quality of the products. Objective: The aim of the study was to develop a MALDI-TOF MS/MS method to characterize the structures of polymerized impurities in cefuroxime axetil drug substance and cefetamet pivoxil drug substance. Methods: Calibrant references were TOF mix, including Angiotensin 2, Angiotensin 1, Glu-1- fibrino, N-Acetyl renin, ACTH 1-17, ACTH 18-39, and ACTH 7-38. Matrix was DHB at a concentration of 10 mg·mL-1. Acetone and water were used as solvents to dissolve cefuroxime axetil and cefetamet pivoxil hydrochloride drug substances, respectively. The prepared solutions were mixed with DHB, volatilized to dry, and subjected to MALDI-TOF MS/MS analysis, respectively. MS data were obtained in the linear mode with a power of 80, and MS² data were obtained in the reflection mode with a power of 120. Molecular weights of polymerized impurities in cefuroxime axetil and cefetamet pivoxil were obtained based on the MS data. Their fragmentation patterns and structural assignments were studied based on the MS² data. Results: Eight polymerized impurities in cefuroxime axetil drug substance and cefetamet pivoxil hydrochloride drug substance made in China were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS/MS), among which impurity 133;-133;¤ were in cefuroxime axetil and impurities 133;¥-133;§ were in cefetamet pivoxil. Based on the experimental results, the polymerization mechanism of polymerized impurities in cephalosporins was discussed. Conclusion: MALDI-TOF MS/MS proved to be simple, quick and sensitive for the analysis of polymerized impurities in cephalosporins.

Aims: This study aims to determine the volatile chemical profile of ethanol-based hand sanitizer marketed in Brazil by HS-SPME/GC-MS. Background: Ethanol-based hand sanitizer has been used to protect against coronavirus disease (COVID-19). In general, these formulations are prepared using a carbomer. In 2020 and 2021, the production of hand sanitizer has increased due to the COVID-19 epidemic. Therefore, it is important to know the composition of this formulation because certain molecules present in some alcoholic mixtures can cause health problems. Methods: Ethanol-based hand sanitizer, AL1, AL2, BL1, CL1, DL1, EL1, FL1, and GL1 (ethanol derivative of fuel station), was purchased from manufacturers commercialized in Araguaína-TO and analyzed by HS-SPME/GC-MS for determining volatile chemical profile. Results: The analyses showed different compositions for the ethanol-based hand sanitizers. Samples AL1 and AL2 contained isopropyl alcohol, ethyl acetate, benzene, ethane-1,1-diethoxy, limonene, and other compounds. Linear alkanes were also detected. Only ethyl acetate and ethane-1,1-diethoxy were detected in CL1, in addition to ethanol. Thus, it is the most suitable sample among those analyzed. The presence of benzene, alkanes, and other hydrocarbons may be associated with the use of fuel ethanol to prepare these sanitizers, as shown in the sample GL1. Benzene, xylene, and toluene were found in FL1. This sample is the most contaminated among those analyzed. Conclusion: The chemical profile of commercial ethanol-based hand sanitizer from eight different samples sold in Araguaína-Brazil was established by GC-MS. Compounds like benzene and other alkanes were found in some samples. These results suggested possible contamination by alcohols unqualified in producing pharmaceutical substances. These analyzes are particularly relevant due to the pandemic situation to avoid COVID-19 proliferation. Benzene and other alkanes are harmful to human health and should be avoided in hand sanitizer production.