Development and validation of an ultrahigh-performance liquid chromatography method for identity, assay and impurity testing of nicotine and preservatives in nicotine nasal spray

Abstract

The topic of this study is to develop and validate an analysis method of nicotine nasal spray produced at McNeil AB. When developing the analysis method, several parameters were determined in advance to make the method more similar to other analysis methods at the company, making it more practical. However, other parameters were adjusted with the aim to improve the resolution and to fulfil the updated cGMP requirements, where category I, II and IV according to USP <1225> were of interest.
The research questions to be answered during this project are; (1) what conditions that leads to the highest resolution, (2) Does these conditions fulfil the cGMP requirements, and (3) if the new method is greener than the currently used method. The aims have been fulfilled by initially varying the temperature, flow, pH and mobile phase gradient by using UHPLC, followed by a full validation where various performance characteristics were studied. Different sequences for the performance characteristics were used for calculations and comparison with the requirements that needed to be fulfilled.
The developed method improved the resolution between the analytes as well as the complexity was decreased. All regulatory requirements were achieved except for the robustness. However, the sample solution was only stable for 45 hours, where the aim was to have a longer stability. Thereby, further investigation should be done on the stability. Also, column equivalence did not fulfil the requirement. The new analysis method was significantly greener, with more than 40 times less consumed solvent.

Conclusion: The developed method showed good results and will be a good implementation for the company, yet further investigations should be done before sending the validation report for approval.

Popular Abstract

Nicotine nasal spray is produced at McNeil AB, with the aim to help people stop smoking, and thereby decrease the deaths caused by smoking. Since nicotine nasal spray is considered as a pharmaceutical product, the analysis of the product needs to fulfil regulatory requirements. Currently used method was issued in the 20th century, which due to an update in the regulatory requirements, also need to be updated. When developing an analysis method of a pharmaceutical product, a validation of the new method is essential to investigate if the requirements are fulfilled.
The method used today was developed year 2019, however this method needed further development before implementation. The aim of this project is to develop this last-mentioned analysis method of nicotine nasal spray, and thereafter to perform a validation by examining various parameters. The analysis method was performed by using ultrahigh-performance liquid chromatography, a commonly used analytical technique. Analytes that were studied were nicotine, which is the active pharmaceutical ingredient, preservatives, and degradants from nicotine. The goal was to find the chromatographic conditions that lead to the best resolution, and to obtain a method that fulfil the regulatory requirements. Also, the new method was aimed to be greener than currently used method.
Overall, this project has been successful where all research questions have been answered. The parameters that were investigated were temperature, flow, pH and gradient of the mobile phase. By using the identified conditions, the new method became greener with a decreased consumption of solvent with more than 40 times. Parameters that were investigated during the validation were: linearity, quantification limit, accuracy, carryover, stability, robustness, precision, specificity, and method equivalence. Also, column equivalence and filter study were investigated. Further investigation should be done regarding the stability and column equivalence, whereas other parameters showed acceptable results. Some advantages of the new method compared to the present method, beyond the less consumed solvent, is the improved accuracy, repeatability, and efficiency, as well as the decreased complexity. Finally, by using the same set-up as other analytical methods at the company, the new method is more practical.

• author: Kandas, Amane
• supervisor: Margareta Sandahl
• organization: Centre for Analysis and Synthesis
• course: KASM01 20211
• year: 2021
• type: M1 - University Diploma
• subject: Chemistry
• keywords: Nicotine, Nicotine nasal spray, Ultrahigh-performance liquid chromatography, Development, Validation, Technical analytical chemistry
• language: English
• id: 9057435
• date added to LUP: 2021-06-28 15:17:02
• date last changed: 2021-06-28 15:17:02