A new rapid ultra‐performance liquid chromatography method for the pharmacokinetic and bioavailability study of diclofenac sodium aqueous injection and lipid microsphere injection in rats

Abstract

A novel, rapid and selective ultra performance liquid chromatography mass spectrometric method had been developed for the pharmacokinetic study of diclofenac sodium (DS) after single intravenous injection of DS aqueous injection and DS lipid microsphere (LM) injection in rats. Ketoprofen (KP) was used as internal standard. Samples were treated by a one-step liquid liquid extraction. Separation was performed on an Acquity UPLC BEH C(18) column (50 x 2.1 mm i.d., 1.7 mum). The mobile phase consisted of acetonitrile-0.1% ammonium hydroxide aqueous solution (20 : 80, v/v) initially in the gradient mode. The detection was carried out by means of electrospray ionization mass spectrometry in negative ion mode with multiple-reaction monitoring mode. Standard curves showed good linearity (r > 0.99) from the plasma concentration of 0.1-50 microg/mL. The lower limit of quantification was 0.1 microg/mL. The intra- and inter-day precisions and the accuracy all satisfied the acceptance criteria. The developed method was validated and successfully applied to the pharmacokinetics study of DS aqueous injection and LM injection. The results showed that the two preparations were bioequivalent in rats.

Comparative in vitro dissolution and in vivo bioequivalence of two diclofenac enteric coated formulations

“…Indifferentstudiesmanymethodsfordeterminationofdiclofenac sodiump lasmac oncentrationsw ereutilized. Among them validated high-performancel iquid chromatography(HPLC) eitherwithUV [1,9], fluorimetric [2], orelectro-chemicaldetection [1,3,5,[10][11][12][13][14][15][16][17];gaschromatography-mass spectrometry [11]a nd thin-layerchromatography(TLC) [5]havebeen reported. Inthisstudythe analyticalprocedurefordetermination of diclofenac sodiuminplasmawasadopted from the method of El-Sayed and co-workers and validated forspecificity,accuracy, precision and sensitivity [18].Forextraction of diclofenac sodium,on 1mlofplasma50 l Lof the internalstandard(200 l g/ m1 of naproxen) and 200 l Lof HCl1Nwasadded,then all sampleswereextracted with5ml hexane/isopropylalcohol (99/1) by vortexing for5min.…”

Pharmacokinetics of felbinac after intravenous administration of felbinac trometamol in rats

“…Injections of NSAIDs such as ketorolac and diclofenac as solutions of various types of salts or in lipid-based vehicles have been extensively used to provide pre-and post-operative analgesia (Seymour et al, 2000;Ong and Tan, 2004;Cui et al, 2010). In some cases, prodrugs such as the ethyl esters of flurbiprofen and felbinac have been developed to treat the severe pain associated with kidney stones and cancer (Nakano et al, 1990;Wu et al, 2009).…”

Herb–drug pharmacokinetic interaction of artificial calculus bovis with diclofenac sodium and chlorpheniramine maleate in rats

“…CPM, 1‐ p ‐chlorophenyl‐1‐(2‐pyridyl)‐3‐dimethylaminopropane maleate, is an alkylamine antihistaminic drug (H 1 RAS) commonly used in the prevention of symptoms of allergic conditions such as rhinitis and urticaria . Although numerous studies on the pharmacokinetics of DS and CPM individually have been carried out, the pharmacokinetic interaction of these two drugs has not yet been reported.…”

“…HPLC‐MS/MS has become increasingly common in the quantitative analysis of drugs owing to its high selectivity and sensitivity, particularly the selected reaction monitoring mode. Many methods have been developed to determine DS and CPM in plasma, among which HPLC‐MS/MS is extensively adopted . However, to our knowledge, no study has reported the simultaneous determination of these two drugs in biological samples by HPLC‐MS/MS.…”