A systematic study on the degradation kinetics (chemical stability) of Gemcitabine injection solution by a stability-indicating liquid chromatography method

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A systematic study of the degradation kinetics (chemical stability) of Gemcitabine Injection solution by a stability-indicating liquid chromatography method
The proposed research study is intended to determine the degradation kinetics of gemcitabine injection solution by applying the stability-indicating liquid chromatography method. This is based on the awareness that kinetics of chemical compounds can be studied when in aqueous solutions with the intention of determining activity at different concentrations. This information would be useful in the formulation of gemcitabine as an antitumor agent that inhibits DNA synthesis to bring about cellular apoptosis (Jansen et al. 885), although Liu, Zhao and Li (1793) it is best used in combination with other antitumor agents. Gemcitabine has been used to treat different cancer forms to include lung, breast, cervical and pancreatic cancers. In this respect, the proposed research study intends to evaluate the degradation characteristics of gemcitabine injection with the intention of identifying the most effective, stable and soluble formulation of the drug to guarantee favorable results.
Gemcitabine has been identified as the compound of interest since it has the potential to counteract cancer effectively. In fact, Anliker et al. (716) report that gemcitabine is active in inhibiting tumor activity by targeting the S-phase of cell growth and replication. By presenting a complete degradation profile of gemcitabine (as intended by the current study), chemistry research will make it possible to present drug formulations that have higher efficacy with longer shelf lives.

It is important to note that degradation kinetics is a useful chemistry tool, particularly in drug formulations where concentrations must be precisely set to guarantee favorable outcomes. An example of this has been presented by Kaijser et al. (1061) where the chemical stability of ifosfamide was analyzed and reported. In this case, the researchers applied stability-indicating high-performance liquid chromatography assay along with UV detection to separate the degradation products with the intention of evaluating the degradation statistics concerning concentration, temperature, ionic strength, buffer composition, and pH as external factors influencing activity (Kaijser et al. 1061).
Salmani et al. (5925) made similar observations when studying the potency and efficacy of thymoquinone as an anticancer medication. By applying HPLC, the researchers were able to evaluate the solubility and stability profiles of the drug. The results indicated that the aqueous solution used had a significant effect on stability and minimal effect on solubility. The study made use of degradation stability to show that the formulation of thymoquinone had an effect on its activity, stability, and effectiveness as an anticancer drug (Salmani et al. 5925). On the other hand, Liu, Zhao and Li (1793) noted that no single chemical analysis approach could be used to present a complete profile of any chemical compound intended for use as a drug. Rather, each approach only focuses on specific aspects of the profile. For instance, microcalorimetry can evaluate thermodynamic, kinetic and half-life properties but adopts a complicated approach that presents the possibility of errors when different subjects are used (Liu, Zhao and Li 1793). The implication is that gemcitabine chemical profile development occurs in progression, with each chemical analysis approach only providing a part of the whole profile. As such, applying stability-indicating liquid chromatography method to evaluate gemcitabine helps in developing its profile as an antitumor medication.
Even as the research proceeds, it is notable that although the kinetic degradation of gemcitabine had previously been studied. An example of this is seen in the case of Jansen et al. (885) where gemcitabine degradation was evaluated, and the results used to develop an Arrhenius plot that would then be extrapolated to estimate the shelf life of different gemcitabine formulations. Anliker et al. (716) conducted similar studies and noted that as an antitumor drug, gemcitabine compounds are typically stable in a solid state at room temperature. Also, it was shown to be more unstable in alkaline solutions than acidic solutions. These results make it clear that it would be preferable to present gemcitabine as a solid or in acidic solutions for solutions. Lia, Zhao and Li (1793) made comparable observations by noting that gemcitabine had a unique half-life, as determined through microcalorimetry.
The results of the proposed studies make it evident that the study of gemcitabine profile is as yet incomplete, requiring additional studies to develop a complete profile. For one, it is clear that gemcitabine should be presented in acid solutions since this is a more stable aqueous form when compare to alkaline solutions. Secondly, the laboratory degradation results can be presented in an Arrhenius plot that is then extrapolated for application in clinical settings. Thirdly, most of the studies have focused on the solid and aqueous forms of gemcitabine and left out injection forms of the gemcitabine. Fourthly, stability-indicating liquid chromatography method can be applied as a novel chemistry evaluation approach to offer a better understanding of gemcitabine injection for application in clinical settings. The proposed research takes the four observations into consideration by adopting stability-indicating liquid chromatography method as a novel approach for evaluating the chemical properties of gemcitabine injection to provide a new perspective.
The research study results will be presented in six chapters that include an introduction, literature review, methodology, results, discussion, and conclusion sections. The introduction section will outline the research problem and theoretical concept. The literature review section will present the results of the secondary data searches. The methodology section will outline the particular approaches applied in collecting both secondary and primary data to include the laboratory outcomes. The results section will outline the primary data analysis outcomes. The discussion section will correlate the results of the secondary and primary data analysis. The conclusion section will present the inferences from the research, possible shortcomings, and recommendations for application in chemistry.
The plan to be applied in the proposed research will involve ten principal steps. Step one will involve formulating a general statement of research objective that is precise, concise and clear. In this case, the study is intended to evaluate the degradation kinetics of Gemcitabine Injection solution using the stability-indicating liquid chromatography method. Step two will entail documenting the precise questions to be answered by the research study. Answering the questions will imply that the set objective has been met. Step three will involve conducting an extensive and exhaustive literature review. Step four will involve deciding on information types that will be pertinent to the study and can answer the questions presented in the second step. Step five will involve designing the laboratory study and matching data analysis. Step six will involve setting up the experiments with the focus being on the stability-indicating liquid chromatography method. Step seven will involve analyzing and manipulating the collected data to point out the relevant trends for degradation kinetics. Step eight will involve presenting the results of the data analysis in figures and tables as a visualization of the outcomes. Step nine will involve drawing rational and consistent inferences from the results. The final step will involve discussing and reporting the results with the intention of making recommendations to influence chemistry practice and research.

Works Cited
Anliker, Sally, Michael McClure, Thomas Briton, Erwin Stephan, Steven Maple and Gary Cooke. ‘Degradation Chemistry of Gemcitabine Hydrochloride, A New Antitumor Agent.’ Journal of Pharmaceutical Science, 83.5(1994), 716.
Jansen, Patrick, Michael Akers, Robert Amos, Steven Baertschi, Gary Cooke, … and Karen McCune. ‘The Degradation of the Antitumor Agent Gemcitabine Hydrochloride in an Acidic Aqueous Solution at pH 3.2 and Identification of Degradation Products.’ Journal of Pharmaceutical Science, 89(2000), 885-891.
Kaijser, G. P., Beijnen, J. H., Bult, A., Hogeboom, M. H. and Underberg, W. J. M. ‘A systematic study on the chemical stability of ifosfamide.’ Journal of Pharmaceutical Biomedical Analysis, 9.10-12(1991), 1061-1067.
Liu, Dai_Huo, Wei-Wei Zhao and Zhong-Xiao Li. ‘To determine the half-life for gemcitabine hydrochloride using microcalorimetry.’ J Therm Anal calorim, 115(2014), 1793-1797.
Salmani, Jumah, Sajid Asghar, Huixia Lv and Jianping Zhou. ‘Aqueous Solubility and Degradation Kinetics of the Phytochemical Anticancer Thymoquinone: Probing the effects of solvents, pH and light.’ Molecules, 19(2014), 5925-5939.