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The established analytical method for determining the concentration of dantrolene sodium (Da) in rat tissues by HPLC/MS/MS technique was successfully applied to tissue distribution studies of Da in rats. Tissue homogenate samples were pretreated by protein precipitation with pre-cooled methanol. Chromatographic separation was achieved on an Acquity HPLC column (Kromat Universil XB-C 18 , 2.1 × 150 mm, 3 μm). Mass spectrometry was conducted with an electrospray ionization interface in negative ionization mode and multiple reaction monitoring was used for quantitative analysis. The results showed that Da was rapidly and widely distributed in tissues and reached the maximum concentration within 0.5 h in all tissues after oral administration of Da-hydroxypropyl-β-cyclodextrin (DHC). It was then metabolized by liver and finally excreted from kidney,which indicated that DHC inclusion complex has better absorption and higher oral bioavailability than Da. The results also provided evidence for the safety and effectiveness of drug clinical application., (© 2019 John Wiley & Sons, Ltd.)

A well-known analgesic (paracetamol, PAR) and skeletal muscle relaxant [dantrolene sodium (DNS)] have been analyzed without interference from their toxic impurities and degradation products. The studied PAR impurities are the genotoxic and nephrotoxic p-amino phenol (PAP) and the hepatotoxic and nephrotoxic chloroacetanilide, while 5-(4-nitrophenyl)-2-furaldehyde is reported to be a mutagenic and carcinogenic degradation product of DNS. The five studied components were determined and quantified by TLC-densitometric and RP-HPLC methods. TLC-densitometry (method 1) used TLC silica gel and chloroform-ethyl acetate-acetic acid-triethylamine (7:3:0.5:0.05, by volume) as the mobile phase with UV scanning at 230 nm, while RP-HPLC (method 2) was based on separation on a C 18 column using methanol-water (55:45, v/v pH 3 with aqueous formic acid) as mobile phase at 1 mL/min and detection at 230 nm. The developed methods were used for determination and quantification of the five studied components in different laboratory-prepared mixtures. The were also applied for analysis of Dantrelax ® compound capsules where no interference among the studied components with each other or from excipients was observed. The methods were validated as per International Conference on Harmonization guidelines, and they compared favorably with the reported ones., (© 2019 John Wiley & Sons, Ltd.)

Six simple, specific, accurate and precise spectrophotometric methods were developed and validated for the simultaneous determination of the analgesic drug; paracetamol (PARA) and the skeletal muscle relaxant; dantrolene sodium (DANT). Three methods are manipulating ratio spectra namely; ratio difference (RD), ratio subtraction (RS) and mean centering (MC). The other three methods are utilizing the isoabsorptive point either at zero order namely; absorbance ratio (AR) and absorbance subtraction (AS) or at ratio spectrum namely; amplitude modulation (AM). The proposed spectrophotometric procedures do not require any preliminary separation step. The accuracy, precision and linearity ranges of the proposed methods were determined. The selectivity of the developed methods was investigated by analyzing laboratory prepared mixtures of the drugs and their combined dosage form. Standard deviation values are less than 1.5 in the assay of raw materials and capsules. The obtained results were statistically compared with each other and with those of reported spectrophotometric ones. The comparison showed that there is no significant difference between the proposed methods and the reported methods regarding both accuracy and precision., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed which can separate and accurately quantitate paracetamol, dantrolene, cetirizine and pseudoephedrine. The method was successfully validated for the purpose of conducting stability studies of the four analytes in quality control (QC) laboratories. The stability-indicating capability of the method was demonstrated by adequate separation of these four analytes from all the degradant peaks. A gradient mobile phase system consisting of (A) 50 mmol L(-1) sodium dihydrogen phosphate, 5 mmol L(-1) heptane sulfonic acid sodium salt, pH 4.2 and (B) acetonitrile was used with Discovery reversed-phase HS C(18) analytical column (250 mm x 4.6 mm i.d., 5 microm particle size). Quantitation was achieved with UV detection at 214 nm, based on peak area. The proposed method was validated and successfully applied for the analysis of pharmaceutical formulations and laboratory-prepared mixtures containing the two multicomponent combinations.

Dantrolene sodium can be determined in plasma and urine samples by high-pressure liquid chromatography without interference from its two major metabolites, the hydroxy and acetamido compounds. The minimum detectability of the drug using this procedure is 8 ng. The complete assay including extraction, evaporation, and separation steps can be performed in approximately 70 min with an accuracy of 1--3%.

A reversed-phase high-performance liquid chromatographic method is described for the simultaneous determination of the skeletal muscle relaxant dantrolene and its metabolites, 5-hydroxydantrolene and nitro-reduced acetylated dantrolene (F-490), in plasma and urine of man and dog. The substances are detected spectrophotometrically at 375 nm. The detection limits are 0.02 mg/l. A preliminary extraction step into a choloroform-butanol mixture is required for the plasma samples. The method is suitable for pharmacokinetic studies of dantrolene.

Operating conditions are described for the qualitative and quantitative determination of dantrolene sodium by high-pressure liquid chromatography. A 10-mum porous silica column was employed, using carbon tetrachloride-dimethylformamide (90:10) as the mobile phase. The flow rate was 2.0 ml/min (1800 psig), and the peaks were detected at 375 nm. The analysis of a dosage form can be carried out within 30 min with an accuracy of 3.1%. The results agree favorably with those obtained with a modified spectrophotofluorometric method.