Development and validation of an HPLC method to determine the stability of fentanyl citrate and bupivacaine hydrochloride mixtures in infusion solutions

Abstract

BackgroundThe use of a combination of different drugs in postoperative analgesia extends the time of analgesia, makes it more efficient and allows the use of lower drug doses, which leads to less risk of side effects and drug dependence. The aim of this study was to develop and validate an HPLC method to determine the stability of fentanyl citrate and bupivacaine hydrochloride mixtures in standard infusion solutions of 0.9% sodium chloride and 5% glucose.MethodsAfter optimisation, the HPLC method parameters were as follows: LiChrospher 100 CN, 250×4 mm (10 µm) column; mobile phase: mixture of acetonitrile and phosphate buffer at pH 2.8 (3:7, V/V) with addition of 0.08 g/l potassium chloride; flow rate: 1.5 ml/min; column temperature: 30°C; spectrophotometric detection at 210 nm. Development of the method involved checking the impact of acetonitrile and KCl concentrations in the mobile phase and choosing the internal standard. Method validation included determining the specificity of the method, its accuracy, linearity, precision, repeatability, limits of detection and quantification.ResultsThe retention times of bupivacaine hydrochloride, fentanyl citrate and procaine hydrochloride, used as an internal standard, were approximately 10 min, 15 min and 5 min, respectively. Method validation confirmed its selectivity, accuracy and precision. The average values of the variation and accuracy coefficients were 0.70% and 99.02% for bupivacaine hydrochloride, and 1.76% and 104.53% for fentanyl citrate. The intermediate precision values were 1.25% for bupivacaine hydrochloride and 1.52% for fentanyl citrate.

Nanocomplex System of Bupivacaine with Dextran Sulfate for Parenteral Prolonged Delivery

“…The drug content in the formulation was determined using highperformance liquid chromatography (HPLC) analysis previous reported, with slight modification. 27 Each sample (100 μL) was diluted 10-fold with a 10 mM phosphate buffer (pH 7.4) and vortexed for 30 min. Then the equivalent volume of methanol was added, then further vortexed for 30 min to extract the BUP.…”

Untitled

“…The HPLC method for the estimation of FC in pharmaceutical dosage forms shows a smaller range of concentrations 7,9 . Table 3.…”

“…The developed method was linear in the range of 0.5 -10 µg ml -1, and the recovery study for this compound was 94.3%. Piekarshi M et al, (2012) developed and validated an HPLC method to determine the stability of fentanyl citrate and bupivacaine hydrochloride mixtures in infusion solutions 9 . The developed method was linear in a range of 2.5 -7.25 µg mL -1 for FC with LOD and LOQ values of 0.5 µg mL -1 and 1.5 µg mL -1 , respectively 9 .…”

“…A few examples of dosage forms of FC currently available in the market in different dosage forms by their trade names are Abstral ® and Fentora ® sublingual tablet; Fentanyl and Fentora ® buccal tablet; Fentanyl citrate injection and Breakyl ® buccal film 6 . A detailed survey of literature revealed that very few analytical methods had been reported for the estimation of FC in dosage formusingHigh Performance Liquid Chromatography (HPLC) 7,8,9,10 . Not even a single spectrophotometric method has been reported for estimation of FC in bulk or pharmaceutical dosage form.…”

“…The UV spectrophotometric method permits analysis of the drug without previous separation and extraction procedures. This alternative is simpler and less expensive than HPLC methods 7,8,9 . The objective of the present study was to develop a simple, precise, accurate and rapid UV spectrophotometric method for the estimation of FC in a pharmaceutical dosage form.…”