A Simple Stability-Indicating UPLC Method for the Concurrent Assessment of Paracetamol and Caffeine in Pharmaceutical Formulations

Abstract

A fixed-dose combination of paracetamol (PCM) and caffeine (CAF) tablets/capsules is the most frequently used over-the-counter medicine for fever and headache. In this paper, a simple, reliable, sensitive, rapid, and stability-indicating ultra-performance liquid chromatography (UPLC) analytical method was proposed for simultaneously assessing PCM and CAF in pharmaceutical formulations. The UPLC method was developed on an Acquity UPLC® CSHTM C18 column, and the column oven temperature was maintained at 35 ± 5 °C with isocratic elution by using a solution of methanol and water (30:70, v/v). The maximum absorbance of PCM and CAF was observed at 272.5 nm. The flow rate was 0.2 mL/min, and the injection volume was 1 µL, with the total run time of 2 min for the separation of PCM and CAF. The proposed UPLC method was validated according to the ICH guidelines, and it demonstrated excellent linearity, with correlation coefficients of 0.9995 and 0.9999 over the concentration ranges of 40–400 and 7–70 ng/mL for PCM and CAF, respectively. The mean retention times of 0.82 ± 0.0 and 1.16 ± 0.02 were observed for PCM and CAF, respectively. The limits of detection and quantification were 16.62 and 3.86 for PCM, respectively, and 50.37 and 11.70 for CAF, respectively. PCM and CAF were subjected to acidic, alkali, oxidative, phytochemical, dry-heat, and wet-heat degradation. The method was found to well separate the analytes’ peaks from degradation peaks, with no alterations in retention times. The proposed method is linear, precise, accurate, specific, and robust, and it can indicate stability and be used for the quantitative assessment of pharmaceutical formulations comprising PCM and CAF within a short period of time.

Develop and Validate a Stability-Indicating HPLC Assay Method for Paracetamol, and parabens in Pharmaceutical Dosages

“…A literature survey revealed the availability of several HPLC methods developed as SIAM to determine PCM in combination with other pharmaceutical drugs such as caffeine [13], methylparaben with carmosine [14], and thiamine and pyridoxal phosphate [15]. In addition, simultaneous analysis of paracetamol in combined pharmaceutical formulations was performed using traditional [16] and multivariate HPLC [17].…”

Validation of HPLC-DAD method for analysis of paracetamol and potassium sorbate in liquid oral formulations and its application to forced degradation study

“…In previously published studies, paracetamol in combination with other active compounds (e.g. caffeine, ibuprofen, trama-dol…) has been determined usually using HPLC methods with C 18 stationary phase, water or buffer combined with methanol or acetonitrile as mobile phase, and UV detection [16][17][18][19][20][21]. These methods were usually applied to quality control of solid dosage forms.…”

Analytical Method Development and Validation Of Stability Indicating RP-HPLC Method For Assay and Related Substances of Paracetamol and Caffeine Effervescent Tablets: Review

“…It can be used quickly to the quantitative evaluation of pharmaceutical formulations containing PCM and CAF and show stability. [17] Binh Thuc Tran et al, This study simultaneously measured the amounts of paracetamol (PAR), ibuprofen (IBU), and caffeine (CAF) in tablets using the classical least-squares (CLS) approach in conjunction with molecular absorption spectrophotometric measurement. With a 0.5 nm step, the absorbance spectra of the standard solutions and samples were measured over this wavelength range.…”