scholarly journals Artifact Peaks Due to Minor Decomposition of Sample Diluent DMSO in Head Space-GC Analysis: Mass Spectrometric Investigation Using Deuterated DMSO and Quadrupole Time-of-Flight Mass Detection

2021 ◽  
Author(s):  
Jinsheng Lin ◽  
Qiang Zhou ◽  
Jun Wang ◽  
Dandan Tang ◽  
Wenquan Zhu ◽  
...  
Keyword(s):  
Method Development ◽  
Formation Mechanisms ◽  
Mass Detection ◽  
Residual Solvents ◽  
Analytical Technique ◽  
Gc Analysis ◽  
Drug Products ◽  
Drug Substances ◽  
Head Space ◽  
Stress Study

<p><b>Rationale: </b>Head space gas chromatography (HS-GC) has become a widely used analytical technique for residual solvents determination in drug substances and drug products. During our method development of residual solvents by HS-GC for certain drug substances, four unknown peaks were observed when dimethyl sulfoxide (DMSO) was employed as sample diluent.</p><p><b>Methods:</b> Use of other sample diluents replacing DMSO did not show these unknown peaks in the HS-GC analysis. HS-GC-MS was then utilized to investigate these peaks. As part of the investigation, DMSO-<i>d<sub>6</sub></i> was used to trace the origins of these unknown peaks to DMSO. A stress study of methanethiol and formic acid was carried out to provide further evidence that <i>S</i>-methyl methanethioate was one of the unknown peaks observed during the original HS-GC analysis.<b></b></p><p><b>Results:</b> The four unknown peaks have been identified as methanethiol, dimethylsulfide, <i>S</i>-methyl methanethioate, and dimethyldisulfide, respectively, and it has been demonstrated that the four peaks are clearly related to DMSO through the use of its deuterated counterpart. Plausible formation mechanisms of these species are proposed.</p><p><b>Conclusions:</b> The occurrence of the peaks is due to minor degradation of DMSO, facilitated by certain drug substances as analytes of the analysis. These peaks are artifacts, rather than genuine impurities of the drug substances. These artifact peaks could widely occur in HS-GC analysis, when DMSO is used as sample diluent.</p>

scholarly journals Artifact Peaks Due to Minor Decomposition of Sample Diluent DMSO in Head Space-GC Analysis: Mass Spectrometric Investigation Using Deuterated DMSO and Quadrupole Time-of-Flight Mass Detection

2021 ◽  
Author(s):  
Jinsheng Lin ◽  
Qiang Zhou ◽  
Jun Wang ◽  
Dandan Tang ◽  
Wenquan Zhu ◽  
...  
Keyword(s):  
Method Development ◽  
Formation Mechanisms ◽  
Mass Detection ◽  
Residual Solvents ◽  
Analytical Technique ◽  
Gc Analysis ◽  
Drug Products ◽  
Drug Substances ◽  
Head Space ◽  
Stress Study

<p><b>Rationale: </b>Head space gas chromatography (HS-GC) has become a widely used analytical technique for residual solvents determination in drug substances and drug products. During our method development of residual solvents by HS-GC for certain drug substances, four unknown peaks were observed when dimethyl sulfoxide (DMSO) was employed as sample diluent.</p><p><b>Methods:</b> Use of other sample diluents replacing DMSO did not show these unknown peaks in the HS-GC analysis. HS-GC-MS was then utilized to investigate these peaks. As part of the investigation, DMSO-<i>d<sub>6</sub></i> was used to trace the origins of these unknown peaks to DMSO. A stress study of methanethiol and formic acid was carried out to provide further evidence that <i>S</i>-methyl methanethioate was one of the unknown peaks observed during the original HS-GC analysis.<b></b></p><p><b>Results:</b> The four unknown peaks have been identified as methanethiol, dimethylsulfide, <i>S</i>-methyl methanethioate, and dimethyldisulfide, respectively, and it has been demonstrated that the four peaks are clearly related to DMSO through the use of its deuterated counterpart. Plausible formation mechanisms of these species are proposed.</p><p><b>Conclusions:</b> The occurrence of the peaks is due to minor degradation of DMSO, facilitated by certain drug substances as analytes of the analysis. These peaks are artifacts, rather than genuine impurities of the drug substances. These artifact peaks could widely occur in HS-GC analysis, when DMSO is used as sample diluent.</p>

scholarly journals Hyphenated Mass Spectrometry versus Real-Time Mass Spectrometry Techniques for the Detection of Volatile Compounds from the Human Body

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7185
Author(s):  
Oliver Gould ◽  
Natalia Drabińska ◽  
Norman Ratcliffe ◽  
Ben de Lacy Costello
Keyword(s):  
Mass Spectrometry ◽  
Volatile Compounds ◽  
Real Time ◽  
Qualitative Data ◽  
Method Development ◽  
Complex Matrices ◽  
Analytical Technique ◽  
Monitoring Drug ◽  
Highly Sensitive ◽  
Insight Into

Mass spectrometry (MS) is an analytical technique that can be used for various applications in a number of scientific areas including environmental, security, forensic science, space exploration, agri-food, and numerous others. MS is also continuing to offer new insights into the proteomic and metabolomic fields. MS techniques are frequently used for the analysis of volatile compounds (VCs). The detection of VCs from human samples has the potential to aid in the diagnosis of diseases, in monitoring drug metabolites, and in providing insight into metabolic processes. The broad usage of MS has resulted in numerous variations of the technique being developed over the years, which can be divided into hyphenated and real-time MS techniques. Hyphenated chromatographic techniques coupled with MS offer unparalleled qualitative analysis and high accuracy and sensitivity, even when analysing complex matrices (breath, urine, stool, etc.). However, these benefits are traded for a significantly longer analysis time and a greater need for sample preparation and method development. On the other hand, real-time MS techniques offer highly sensitive quantitative data. Additionally, real-time techniques can provide results in a matter of minutes or even seconds, without altering the sample in any way. However, real-time MS can only offer tentative qualitative data and suffers from molecular weight overlap in complex matrices. This review compares hyphenated and real-time MS methods and provides examples of applications for each technique for the detection of VCs from humans.

Review on Pharmaceutical Co-Crystals and Design Strategies

2021 ◽  
pp. 175-180
Author(s):  
A.V.S. Ksheera Bhavani ◽  
A. Lakshmi Usha ◽  
Kayala Ashritha ◽  
Radha Rani E.
Keyword(s):  
Aqueous Solubility ◽  
Active Pharmaceutical Ingredient ◽  
Crystal Formation ◽  
Stoichiometric Ratio ◽  
Design Strategies ◽  
Great Opportunity ◽  
Drug Products ◽  
Drug Substances ◽  
Component Systems ◽  
Physical And Chemical

Poor aqueous solubility and low oral bioavailability of an active pharmaceutical ingredient are the major constraints during the development of new product. Various approaches have been used for enhancement of solubility of poorly aqueous soluble drugs, but success of these approaches depends on physical and chemical nature of the molecules being developed. Co-crystallization of drug substances offers a great opportunity for the development of new drug products with superior physicochemical such as melting point, tabletability, solubility, stability, bioavailability and permeability, while preserving the pharmacological properties of the active pharmaceutical ingredient. Co-crystals are multi component systems in which two components, an active pharmaceutical ingredient and a coformer are present in stoichiometric ratio and bonded together with non-covalent interactions in the crystal lattice. This review article presents a systematic overview of pharmaceutical co-crystals, differences between co-crystals with salts, solvates and hydrates are summarized along with the advantages of co-crystals with examples. The theoretical parameters underlying the selection of coformers and screening of co-crystals have been summarized and different methods of co-crystal formation and evaluation have been explained.

Analytical Method Development and Validation of Glipizide to Determine Residual solvents by head Space-Gas Chromatography

2021 ◽  
pp. 2440-2444
Author(s):  
Sanapala Srinivasa Rao ◽  
A. Vijayalakshmi
Keyword(s):  
Gas Chromatography ◽  
Method Development ◽  
Limit Of Detection ◽  
Dimethyl Formamide ◽  
Analytical Methodology ◽  
Residual Solvents ◽  
Flame Ionization ◽  
Ich Guidelines ◽  
Method Development And Validation ◽  
Development And Validation

Residual solvents in Pharmaceuticals are termed as organic volatile impurities. These are the chemicals that are used in the manufacture of drug substance or excipients or use in the preparation of final formulation. Most of the available methods use liquid chromatography which could be expensive and time consuming. Hence, an analytical methodology was developed for the quantification of residual solvents in Glipizide using a headspace gas chromatography (HSGC) with the help of flame ionization detector (FID). Methanol, acetone and dimethyl formamide as residual solvents were determined in Glipizide. Analysis was performed by headspace GC/FID method on Auto system- HS40. Nitrogen was used as a carrier gas and the separation of residual solvents was achieved by DB-Wax 0.25mm, 0.3mcm column. The thermostat temperature was 115 °C for 40 minutes for each vial. % RSD for nine injections obtained are in acceptance criteria. The correlation coefficient R2 obtained greater than 0.99. The method parameters were validated includes specificity, limit of detection and quantification, accuracy, linearity, precision, and robustness. According to the International Conference on Harmonization (ICH) guidelines, a new simple, specific, accurate and precise method was developed and validated.

scholarly journals METHOD DEVELOPMENT AND VALIDATION OF LERCANIDIPINE IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY TANDEM-MASS SPECTROMETRY

2018 ◽  
Vol 10 (4) ◽  
pp. 87
Author(s):  
Yahdiana Harahap ◽  
Norma Andriyani ◽  
Harmita .
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Method Development ◽  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Tandem Mass ◽  
Mass Detection ◽  
Column Temperature ◽  
Z Value

Objective: To obtain an optimum and validated method for analyzing lercanidipine in plasma using Ultra Performance Liquid Chromatography of Tandem Mass Spectrometry (UPLC-MS/MS).Methods: The separation was carried out using 1.7μm (2.1 x 100 mm) Waters AcquityTM UPLC C18 column, a mobile phase of the 0.1% formic acid-methanol mixture (20:80 v/v) with isocratic elution, 30 °C column temperature, 0.2 ml/min flow rate and amlodipine as an internal standard. Mass detection was performed with a positive XBL TQD type Electrospray Ionization (ESI) in Multiple Reaction Monitoring modes. Lercanidipine was detected at m/z value of 612.11>280.27 and amlodipine was detected at m/z value 409.1>238.15. The optimum sample preparation method was a liquid-liquid extraction using 5 ml of n-hexane-ethyl acetate (50:50 v/v), vortex mixed for 3 min, centrifuged at 4000 rpm for 20 min, evaporated with nitrogen at 50 °C for 30 min, and the residue was reconstituted with 100 μl of mobile phase.Results: The method was linear in the range of 0.025-10 ng/ml with r ≥ 0.9986. Accuracy and precision within-run and between-run met the requirements with %diff and %CV, not exceeding ± 15% and not more than ± 20% for Lower Limit of Quantification (LLOQ) concentration.Conclusion: It was concluded that the developed method met the requirements of selectivity, carry over, stability, the integrity of dilution, and matrix effects under the Guideline on Bioanalytical Method Validation by the European Medicines Agency in 2011. 

Sign in / Sign up

Export Citation Format

Share Document