Development and validation of an HPLC assay for fentanyl and related substances in fentanyl citrate injection, USP

Lambropoulos, John; Σπανός, Γ.; Lazaridis, Nick V.; Ingallinera, Thomas S.; Rodriguez, Vonda K.

doi:10.1016/s0731-7085(99)00077-1

Cited by 38 publications

(24 citation statements)

References 2 publications

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“…The implementation of 201 nm as detection wavelength was considered after practically achieving better sensitivity. Additionally, the UV spectrum of FEN in mobile phase showed two maximum absorption peaks at 210 nm and 258 nm, these results are consistent with the previously reported methods that are using detection wavelengths ranging from 200-210 nm [6,7,8].…”

Section: Chromatographysupporting

confidence: 92%

“…Due to variation of FEN use, misuse and its high potency; several studies have been reported for its detection in biological samples and different body organs using various separation and detection techniques including highperformance liquid chromatography (HPLC) coupled to tandem mass spectroscopy [5], and some other HPLC-UV methods [6,7,8]. These methods included different types of extraction procedures such as liquid-liquid extraction (LLE) utilizing hexane to extract target analytes [6,7], solid phase extraction (SPE) [9] and single-drop liquid-liquid-liquid micro-extraction (LLME) [10].…”

Section: Introductionmentioning

confidence: 99%

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HPLC-UV method development for fentanyl determination in rat plasma and its application to elucidate pharmacokinetic behavior after i.p. administration to rats

Almousa

Ikeda

Wada

et al. 2011

Journal of Chromatography B

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A simple, rapid and validated high performance liquid chromatography method with UV detection for the quantification of an opioid agonist, fentanyl (FEN), in rat plasma was developed. The assay procedure involved chromatographic separation using a ZIC-HILIC SeQUANT column (250 × 4.6 mm, i.d., 5 µm) and a mobile phase of acetonitrile and acetate buffer (pH 3.4, 20 mM) of ratio (= 65:35, v/v) at a flow rate of 1.2 mL/min and detection wavelength of 201 nm. Plasma sample (100 μL) pretreatment was based on simple deprotienization by acetonitrile spiked with clonidine as an internal standard (I.S.) of 20 ng/mL followed by extraction with tert-butyl methyl ether and centrifugation. The organic layer was evaporated under N 2 gas and reconstituted with 100 μL of acetate buffer (pH 3.4, 20 mM), and 50-μL portions of reconstituted sample were injected onto the column. Sample analysis including sample pretreatment was achieved within 35 min. Calibration curve was linear (r ≥ 0.998) from 5 to 100 ng/mL. Both intra-and inter-day assay precisions that are presented through R.S.D were lower than 12.6% for intra-day and lower than 12.0% for inter-day assessment. Limit of detection was 0.8 ng/mL at S/N of 3. This method was omitting the use of expensive solid phase extraction and time consuming liquid extraction procedures. Moreover, the present method was successfully applied to study pharmacokinetic parameters of FEN after intraperitoneal administration to male Wistar rat. Pharmacokinetic parameters estimated by using moment analysis were; T 1/2 198.3 ± 44.7 min, T max 28.3 ± 2.9 min and AUC 0-180 15.6 ± 2.9 (×10 2 ) ng·min/mL.

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Section: Chromatographysupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

HPLC-UV method development for fentanyl determination in rat plasma and its application to elucidate pharmacokinetic behavior after i.p. administration to rats

Almousa

Ikeda

Wada

et al. 2011

Journal of Chromatography B

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“…Estudos de estabilidade revelam que a fentanila é uma molécula lábil, principalmente quando em solução aquosa e sob exposição à luz (7)(8)(9). Portanto, é indicado que o produto seja mantido em temperatura ambiente e protegido da luz.…”

Section: Resultsunclassified

Investigação Da Suspeita De Desvio De Qualidade Em Uma Solução Injetável De Citrato De Fentanila

Lombardo

Eserian

2015

Infarma

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Investigação da suspeita de desvio de qualidade em uma solução injetável de citrato de fentanilaInvestigation of a quality deviation occurrence on a fentanyl citrate solution for injection ABSTRACT Fentanyl is a pain reliever drug for hospital use mainly indicated as an anesthesia adjunct. Due to a complaint made by a hospital located in São Paulo, related to therapeutic failure of an injectable solution containing fentanyl citrate after use in anesthesia, samples of the product were collected for analysis by health services. The objective of this study was to perform physico-chemical tests on the samples, with priority to quantification and drug identification, using a high performance liquid chromatograph couppled with diode array detector. The two batches analyzed showed positive identification of fentanyl citrate and 97.30% of the drug content; these results were in accordance to recommended range by the product manufacturer. Thus, it was possible to exclude deviations in the drug content as the cause for therapeutic inefficacy, indicating the need for additional investigation and raising further discussion of the case.Keywords: Analysis of Products; Fentanyl; Chromatography, Liquid; Dosage RESUMO A fentanila é um fármaco analgésico de uso hospitalar indicado principalmente como componente da anestesia. Devido a uma queixa técnica de um hospital de São Paulo apontando a ineficácia terapêutica de uma solução injetável de citrato de fentanila após o uso na anestesia, amostras do produto foram coletadas pela Vigilância Sanitária para análise. O objetivo deste trabalho foi realizar ensaios físico-químicos nas amostras, com prioridade para identificação e teor do fármaco, utilizando um cromatógrafo líquido de alta eficiência equipado com detector de arranjo de diodos. Os dois lotes analisados apresentaram identificação positiva para citrato de fentanila e 97,30% do teor declarado do fármaco; resultados satisfatórios em relação ao especificado pelo fabricante do produto. Assim, foi possível excluir desvios no teor do fármaco como a causa da ineficácia terapêutica, indicando a necessidade de investigações complementares e levantando maiores discussões sobre o caso.

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“…It was found to decompose under heat, light, acid, alkaline or oxidant conditions (LAMBROPOULOS et al,1999;GARG et al, 2010;QI et al, 2011). N-phenyl-1-(2-phenylethyl)-piperidin-4-amine (PPA) is suggested by some authors as a potentially genotoxic degradation product of fentanyl, probably attributted to the presence of the aromatic amino group (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…Garg et al (2010) demostrated that the exposure of fentanyl powder to white fluorescent light and a very intense UV radiation for 7 days was not sufficient to degrade the drug [5]. On the other hand, the previous study conducted by Lambropoulos et al (1999) revealed a significant decrease in the drug amount and the formation of ten degradation products, including PPA, after exposure of fentanyl aqueous solution to UV chamber (254 nm), for 13 days.…”

Section: Introductionmentioning

confidence: 99%

Determination of Fentanyl in Injection Solution Exposed to Improper Storage Conditions

Lombardo

Eserian

2018

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RESUMOA estabilidade de medicamentos consiste no potencial do produto em preservar as especificações de qualidade em toda a cadeia de suprimento. Embora esforços devam ser realizados para aprimorar a estabilidade da formulação, algumas precauções podem ser requeridas para minimizar fatores externos que afetem características físico-químicas determinantes da eficácia e segurança do produto. Neste trabalho, uma solução injetável de citrato de fentanila foi submetida a diferentes esquemas de fotoexposição a curto prazo, a fim de simular possíveis desvios no manuseio e armazenamento do produto durante a rotina hospitalar. O teor do fármaco foi avaliado por cromatografia líquida de alta eficiência em fase reversa (CLAE-FR), utilizando um detector de fotodiodos. Os resultados indicaram que o teor de fentanila foi satisfatório, mesmo após a exposição das ampolas à luz solar ou à luz artificial por 18 horas. Estudos futuros se fazem necessários para avaliar o efeito de condições ambientais adversas sobre a solução injetável de fentanila.Palavras-chave: Fentanila; Estabilidade de Medicamentos; Armazenamento de Medicamentos. 2 ABSTRACTStability of drugs consists of the product`s potential to preserve the quality specifications within the entire supply chain. Although efforts should be taken to improve the formulation stability, some precautions may be required to minimize external factors affecting physicochemical characteristics that determine product's effectiveness and safety. In this work, fentanyl citrate injection solution has been subjected to different schemes of short-term photoexposure, in order to simulate possible deviations in the handling and storage of the product during the hospital routine. Drug potency was evaluated by reversed-phase highperformance liquid chromatography (RP-HPLC), using a photodiode array detector. The results indicated that the amount of fentanyl was satisfactory even after the exposure of the ampoules to sunlight or artificial light for 18 hours. Further studies are needed to evaluate the effect of adverse environmental conditions on fentanyl injection.

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Development and validation of an HPLC assay for fentanyl and related substances in fentanyl citrate injection, USP

Cited by 38 publications

References 2 publications

HPLC-UV method development for fentanyl determination in rat plasma and its application to elucidate pharmacokinetic behavior after i.p. administration to rats

HPLC-UV method development for fentanyl determination in rat plasma and its application to elucidate pharmacokinetic behavior after i.p. administration to rats

Investigação Da Suspeita De Desvio De Qualidade Em Uma Solução Injetável De Citrato De Fentanila

Determination of Fentanyl in Injection Solution Exposed to Improper Storage Conditions

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