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Application of the HPLC Method in Parenteral Nutrition Assessment: Stability Studies of Ondansetron

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Application of the HPLC Method in Parenteral Nutrition Assessment: Stability Studies of Ondansetron processes Article Application of the HPLC Method in Parenteral Nutrition Assessment: Stability Studies of Ondansetron Szymon Tomczak * , Vera Radwan , Anna Jeli ´nskaand Maciej Stawny Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 6 Grunwaldzka, 60-780 Pozna´n,Poland; [email protected] (V.R.); [email protected] (A.J.); [email protected] (M.S.) * Correspondence: [email protected]; Tel.: +48-618-546-617 Abstract: Ondansetron (OND) is a serotonin type 3 receptor antagonist that exhibits antiemetic activity. From the clinical point of view, vomiting and nausea prevention is an important task. Anticancer treatment and recovery impact the patient’s overall state by affecting appetite, well-being, and physical activity, and consequently, nutrition quality. Depending on the patient’s indication and condition, parenteral nutrition is administered to meet full nutritional requirements. In addition, antiemetic drugs can be added to the parenteral nutrition (PN) admixture to treat chemo- or radio-therapy-induced nausea and vomiting. However, adding any medication to the PN admixture can result in the instability of the composition in the overall admixture. This study aimed to develop the HPLC method of determination of OND in Lipoflex special, one of the most popular, ready-to-use PN admixtures. The proposed HPLC method and the sample preparation procedure were suitable for analyzing OND in PN admixture stored under various conditions, such as exposure to sunlight and temperature. It was found that the decomposition of OND during the seven-day storage did not exceed 5% and did not depend on external factors. Based on the conducted research, it is recommended to add OND to Lipoflex special, and it is Citation: Tomczak, S.; Radwan, V.; possible to store such an admixture for seven days. Jeli´nska,A.; Stawny, M. Application of the HPLC Method in Parenteral Keywords: drug determination; parenteral nutrition; stability study; ondansetron; HPLC Nutrition Assessment: Stability Studies of Ondansetron. Processes 2021, 9, 453. https://doi.org/ 10.3390/pr9030453 1. Introduction Ondansetron (OND) is a serotonin (5-hydroxytryptamine) type 3 receptor antagonist Academic Editors: Malgorzata Starek that exhibits antiemetic activity. The drug belongs to a carbazole derivative containing and Monika D ˛abrowska nitrogen and carbon rings [1]. The chemical structure is presented in Figure1. It is struc- turally similar to serotonin, which allows it to bind selectively to the 5-HT receptors. OND Received: 31 January 2021 3 is indicated as an effective antiemetic agent and is used for the prevention of nausea and Accepted: 25 February 2021 Published: 3 March 2021 vomiting in a variety of situations, including chemo- and radiotherapy, postoperative and pregnancy-induced nausea and vomiting [2,3]. From the clinical point of view, vomiting Publisher’s Note: MDPI stays neutral and nausea prevention is an important task. Anticancer treatment and recovery impact the with regard to jurisdictional claims in patient’s overall state by affecting appetite, well-being, physical activity, and consequently, published maps and institutional affil- nutrition quality. There are situations when malnutrition negates recovery prospects, iations. because therapy has to be postponed due to the patient’s condition. Therefore, proper nutrition is key to successful treatment. As far as signs of malnutrition or body mass loss are concerned, each may indicate the onset of cancer and concern healthcare profession- als, since a lack of nutritional intervention may compromise the patient’s condition and negatively influence prognosis. When malnutrition occurs, clinical nutrition remains neces- Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. sary to support the recovery process. Depending on the state of the patient’s health and This article is an open access article resulting nutritional needs, it is necessary to administer either oral (regular or therapeutic distributed under the terms and diet), enteral, or parenteral nutrition (EN or PN) [4,5]. Nutritional treatment of severely conditions of the Creative Commons malnourished patients has become routine in most modern-day hospitals. Depending on Attribution (CC BY) license (https:// th e patient’s indication and condition, parenteral nutrition is administered to meet full creativecommons.org/licenses/by/ nutritional requirements. For instance, cancer patients receiving anticancer therapy such 4.0/). as chemotherapy or radiotherapy cannot eat food enterally due to consistent nausea and Processes 2021, 9, 453. https://doi.org/10.3390/pr9030453 https://www.mdpi.com/journal/processes Processes 2021, 9, x FOR PEER REVIEW 2 of 12 Processes 2021, 9, 453 2 of 12 meet full nutritional requirements. For instance, cancer patients receiving anticancer ther- apy such as chemotherapy or radiotherapy cannot eat food enterally due to consistent nausea and vomiting from the anticancer drugs. Therefore, parenteral nutrition can be administeredvomiting from to the provide anticancer nutritional drugs. support Therefore, in these parenteral types nutritionof patients. can Antiemetic be administered drugs, suchto provide as OND nutritional, can also support be added in theseto the types PN admixture of patients. to Antiemetic treat chemo drugs,- or radiotherapy such as OND,- inducedcan also nausea be added and to vomiting. the PN admixture The addition to treat of OND chemo- to the or parenteral radiotherapy-induced nutrition admixture nausea canand reduce vomiting. the Therisk additionof catheter of- ONDrelated to infections. the parenteral However, nutrition adding admixture any drug can to reduce the par- the enteralrisk of catheter-relatednutrition admixture infections. can result However, in the instability adding any of drugthe admixture to the parenteral’s overall nutrition compo- sitionadmixture. can result in the instability of the admixture’s overall composition. Figure 1. OndansetronOndansetron hydrochloride di dihydrate—chemicalhydrate—chemical structure structure.. PN admixture admixture consists consists of of various various ingredients ingredients of high of high chemical chemical reactivity reactivity (water, (water, glu- cose,glucose, amino amino acids, acids, lipids, lipids, trace elements, trace elements, electrolytes, electrolytes, and vitamins) and vitamins) co-existing co-existing in one con- in tainer.one container. It is important It is important to note tothat note the that PN theadmixture PN admixture is an oil is-in an-water oil-in-water emulsion, emulsion, which explainswhich explains its thermodynamic its thermodynamic sensitivity. sensitivity. The physicochemical The physicochemical compatibility compatibility of PN admix- of PN turesadmixtures is another is another vital feature vital featurein the clinical in the clinicalpoint of pointview. ofHospitalized view. Hospitalized patients often patients re- ceioftenve receivedrugs via drugs an intravenous via an intravenous route alongside route alongside nutritional nutritional supplementation. supplementation. An addi- An tionaladditional challenge challenge then then results results from from the the need need to toensure ensure an an appropriate appropriate therapy therapy,, especially especially when several drugs are administered simultaneously [[6]6].. The method of high high-performance-performance liquid chromatography (HPLC) (HPLC) has has been been success- success- fullyfully used used in in the analysis of of a aminomino acids and vitamins added added to to the the PN PN admixtures. admixtures. Vazquez et al. [[7]7] developeddeveloped thethe simultaneoussimultaneous determination of thirteen vitamins using thethe HPLC HPLC-UV-MS-MS-UV-MS-MS method. The The need need for for tandem mass spectrometry was due to the UV dete detector’sctor’s low low selectivity selectivity and and the the lack lack of of a suitable chromophore for some vitamins, such as as pantothenic pantothenic acid. acid. Ribeiro Ribeiro et et al. al. [8] [8 ]examined examined vitamin vitaminss B1 B1 and and B6 B6 by by HPLC HPLC using using a photodiodea photodiode array array detector. detector. These These researchers researchers used used fluorimetry fluorimetry to determine to determine vitamin vitamin B2, andB2, andthe vitamin the vitamin C content C content was wasdetermined determined by iodometric by iodometric titration. titration. HPLC HPLC was also was used also toused determine to determine cocarboxylase cocarboxylase [9], vitamins [9], vitamins A and A E and [10] E, and [10], dehydroascorbic and dehydroascorbic acid [11] acid. [The11]. methodsThe methods of chromatographic of chromatographic separation separation and and determin determinationation of vitamin of vitaminss B1 B1[12,13] [12,13 and] and C [14]C[14 and] and drugs drugs,, such such as ranitidine as ranitidine [13] [,13 linezolid], linezolid [15], [ 15cefepime], cefepime [16], [ceftazidime16], ceftazidime [17], [am-17], picillinampicillin [18] [,18 and], and ciprofloxacin ciprofloxacin [19] [ 19in] PN in PN admixtures admixtures were were also also described. described. Several bioanalytical bioanalytical methods methods have have been been reported reported in the in theliterature literature for the for quantifica- the quan- tiontification of OND of OND,, for example for example,, spectrophotometric spectrophotometric [20] and [20 more] and popular more popular liquid liquidchromatog- chro- matography with UV [21–24] or MS [25–29] detection. Raza et al. [20]
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