Sensitive and selective LC‐MS/MS for the determination of tolperisone and etodolac in human plasma and application to a pharmacokinetic study

Abstract

Tolperisone and etodolac were proven to have synergistic effect for patients of acute low back pain associated with musculoskeletal spasm. In this work, a specific, highly sensitive and reproducible analytical method was developed and validated for the simultaneous determination of tolperisone and etodolac in human plasma using liquid chromatography-tandem mass spectrometric technique. Liquid-liquid extraction was optimized for sample preparation. Zorbax C 8 column (3.5 μm, 50 × 4.6 mm) was used, carrying a mobile phase mixture of 10.0 mM ammonium formate:acetonitrile (40:60, v/v) pH 3.8, running in an isocratic mode. Chlorzoxazone acted as an internal standard. Sample volume of injection was 5.0 μL, and analysis was achieved within 2.5 min. Detection and quantitation were performed by electrospray ionization mass spectrometry using the multiple-reaction monitoring mode. The proposed method could determine the analytes in the range of concentration 0.5-200.0 ng mL −1 for tolperisone and 0.05-20.0 μg mL −1 for etodolac. Findings of inter-and intraday precisions were ≤12.3% with accuracy of ±5.0%. Pharmacokinetics study for the two drugs after oral administration of healthy human volunteers was achieved with the aid of application of the developed study.

Screen-printed sensors for efficient potentiometric analysis of tolperisone hydrochloride in presence of its co-formulated drugs

“…Fig. 1 Chemical structure of TOLP not accessible in most laboratories for routine analysis [4][5][6][7][8]. Potentiometric ion-selective electrode (ISE) is a cost-effective analytical technique that can be employed for performing measurements in colored and turbid solutions [9,10].…”

“…Literature review revealed that some analytical techniques such as chromatographic methods [3][4][5][6] and UV Spectrophotometry [7,8] had been reported for estimation of TOLP in individual dosage forms and combination with other drugs. Even though good results were achieved, the proposed techniques are solvent and time-consuming and use costly instruments which are…”

“…Literature review revealed that some analytical techniques such as chromatographic methods [ 3 – 6 ] and UV Spectrophotometry [ 7 , 8 ] had been reported for estimation of TOLP in individual dosage forms and combination with other drugs. Even though good results were achieved, the proposed techniques are solvent and time-consuming and use costly instruments which are not accessible in most laboratories for routine analysis [ 4 – 8 ]. Potentiometric ion-selective electrode (ISE) is a cost-effective analytical technique that can be employed for performing measurements in colored and turbid solutions [ 9 , 10 ].…”

A liquid chromatography‐tandem mass spectrometry method for comprehensive determination of metabolites in the purine pathway of rat plasma and its application in anti‐gout effects of Lycium ruthenicum Murr.

“…However, the classic methods of purine detection, such as ion exchange chromatography and reversed-phase-high-performance liquid chromatography (RP-HPLC) were not superior in sensitivity and specificity [13,14]. Therefore, LC-MS was considered and preferred owing to the complexity of the compounds in plasma [15,16]. Yamaoka et al [17] have established a reproducible and accurate ultra-performance LC (UPLC)-MS method to simultaneously quantify 23 nucleotides, which was not suitable for large-scale detection due to its long running time, and the switching of positive and negative ion modes would bring fluctuations in sensitivity.…”

“…However, the classic methods of purine detection, such as ion exchange chromatography and reversed‐phase–high‐performance liquid chromatography (RP‐HPLC) were not superior in sensitivity and specificity [13, 14]. Therefore, LC‐MS was considered and preferred owing to the complexity of the compounds in plasma [15, 16]. Yamaoka et al.…”