A high performance liquid chromatography–tandem mass spectrometric method for the determination of mefenamic acid in human plasma: application to pharmacokinetic study

Abstract

In the present study, the development and validation of an LC-MS/MS method for quantifying mefenamic acid in human plasma is described. The method involves liquid-liquid extraction using diclofenac as an internal standard (IS). Chromatographic separation was achieved on a Thermo Hypurity C(18) , 50 × 4.6 mm, 5 µm column with a mobile phase consisting of 2 m m ammonium acetate buffer and methanol (pH 4.5 adjusted with glacial acetic acid; 15:85, v/v) at a flow-rate of 0.75 mL/min and the total run time was 1.75 min. Analyte was introduced to the LC-MS/MS using an atmospheric pressure ionization source. Both the drug and IS were detected in negative-ion mode using multiple reaction monitoring m/z 240.0 → 196.3 and m/z 294.0 → 250.2, respectively, with a dwell time of 200 ms for each of the transitions. The standard curve was linear from 20 to 6000 ng/mL. This assay allows quantification of mefenamic acid at a concentration as low as 20 ng/mL in human plasma. The observed mean recovery was 73% for the drug. The applicability of this method for pharmacokinetic studies has been established after successful application during a 12-subject bioavailabity study.

Screening of non‐steroidal anti‐inflammatory drugs for inhibitory effects on the activities of six UDP‐glucuronosyltransferases (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using LC‐MS/MS

“…Based on our findings, diclofenac and mefenamic acid might be used as a general UGT inhibitor. Median plasma maximum concentrations (9.04 μM) of mefenamic acid after a single dosage of mefenamic acid (250 mg) in human were higher than the inhibitory potential (IC 50 = 3.6 μM) of mefenamic acid on UGT2B7 [29]. However, plasma concentrations do not reflect liver tissue concentrations.…”

Development of an eco‐friendly fluorescent probe for mefenamic acid sensing in pharmaceuticals and biofluids

“…MFA is administered orally as film‐coated tablets or capsules, with either 250 or 500 mg/unit dose three times a day, and maximum plasma MFA concentration of 2200 ng/mL is achieved within 2–6 h of administration. About 50% of the dose is recovered in urine either unchanged or as metabolite conjugates [2, 4]. MFA, as all NSAIDs, exerts its therapeutic action through the inhibition of the enzyme COX preventing the synthesis of prostaglandins that mediate pain and other diseases [5].…”

LC-MS/MS methodology development and validation for the screening and quantification of five antibiotics in water

“…Recently, these multi-class multi-residue methods have been introduced to further increase the monitoring efficiency. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] From previous research, there are no simultaneously analytical methodology in only one extraction and analytical detection for the selected four class antibiotics.…”