An improved LC–MS/MS method for the quantification of alverine and para hydroxy alverine in human plasma for a bioequivalence study / 药物分析学报

A highly sensitive and selective high performance liquid chromatography–tandem mass spectrometry method was developed and validated for the quantification of alverine (ALV) and its active metabolite, para hydroxy alverine (PHA), in human plasma. For sample preparation, solid phase extraction of analytes was performed on Phenomenex Strata-X cartridges using alverine-d5 as the internal standard. The analytes were separated on Symmetry Shield RP18 (150 mm×3.9 mm, 5 μm) column with a mobile phase consisting of acetonitrile and 10 mM ammonium formate (65:35, v/v). Detection and quantitation was done by electrospray ionization mass spectrometry in the positive mode using multiple reaction monitoring. The assay method was fully validated over the concentration range of 15.0–15,000 pg/mL for ALV and 30.0–15,000 pg/mL for PHA. The intra-day and inter-day accuracy and precision (%CV) ranged from 94.00%to 96.00%and 0.48%to 4.15%for both the analytes. The mean recovery obtained for ALV and PHA was 80.59% and 81.26%, respectively. Matrix effect, expressed as IS-normalized matrix factor ranged from 0.982 to 1.009 for both the analytes. The application of the method was demonstrated for the specific analysis of ALV and PHA for a bioequivalence study in 52 healthy subjects using 120 mg ALV capsules. The assay reproducibility was also verified by reanalysis of 175 incurred subject samples.

Sertraline hydrochloride combined with compound alverine citrate in the treatment of irritable bowel syndrome / 中国基层医药

Objective To observe the clinical efficacy of sertraline hydrochloride combined with compound alverine citrate in the treatment of irritable bowel syndrome(IBS).Methods 72 patients with IBS were randomly divided into control group and combined treatment group.The control group received a 10 -week course of twice daily 60mg compound alverine citrate singly.The combined treatment group received a 10 -week course of twice daily 60mg compound alverine citrate and thrice daily 50mg sertraline hydrochloride.The change of clinical efficacy and the score of abdominal pain,abdominal bulge,diarrhea,rectal and anal uncomfortableness were assessed before and after the treatment.Results The total clinical efficacy rate was 55.55% in the control group and 88.88% in the combined treatment group,the difference was statistically significant(χ2 =10.225,P <0.05).The scores of abdominal pain, abdominal bulge,diarrhea, rectal and anal uncomfortableness in the control group were (4.91 ±1.12) points, (3.55 ±0.45) points,(1.59 ±0.49) points,(1.86 ±0.26) points,which in the combined treatment group were (0.95 ±0.46)points,(1.08 ±0.51)points,(0.89 ±0.71) points,(1.12 ±0.35) points.The combined treatment group were significantly improved compared with the control group after 8 weeks treatment( t =10.314,10.264, 9.561,9.823,all P <0.05).Conclusion The clinical efficacy of sertraline hydrochloride combined with compound alverine citrate is more efficient on IBS,it is worth to extend and apply in clinic.

Method Development for Quantification of Donor-Acceptor Complexes of Alverine Citrate and Tapentadol by Visible Spectrophotometry.

In this present work two colorimetric methods were developed based on donor-acceptor complexes of alverine citrate (ALV) and tapentadol (TAP) with cobalt thiocyanate. These methods were developed on Perkin Elmer LAMBDA 25 UV–VIS spectrophotometer with 1cm quartz cells. The colored species formed are the coordination complexes of the drugs (electron donor) and the central metal atom of cobalt thiocyanate (electron acceptor) which is extractable into nitrobenzene from aqueous solution. The reaction conditions were optimized and validated to achieve maximum colour intensity. The colored complexes show maximum absorbance measured at 625 nm for both ALV and TAP. The absorbances were found to increase linearly with an increase in concentration which was corroborated by the calculated regression coefficients (0.9998-0.9999). Linearity was obeyed in the range of 100-600 μg/ml for both ALV and TAP, respectively. The molar absorptivity, sandell’s sensitivity, LOD, LOQ and other validation parameters have been evaluated extensively as per ICH guidelines and all the parameters were found within the acceptance criteria for both methods. The proposed methods were proven to be more accurate, simple, precise and rapid by statistical validation of recovery studies and could be suitable for regular analysis.

A case report of alverine-citrate-induced acute hepatitis / 대한간학회지

Alverine citrate is one of the most commonly used antispasmodic drugs for patients with irritable bowel syndrome. Alverine-citrate-induced hepatotoxicity is extremely rare, with only a few cases having been reported worldwide. We present a case of a 75-year-old female patient who experienced complicated jaundice and abdominal discomfort after taking alverine citrate. Other causes of hepatitis were ruled out and the results of the liver function test returned to normal after ceasing the drug. This is the first case report in Korea of alverine-citrate-induced hepatotoxicity.