Development and validation of a high throughput UPLC–MS/MS method for simultaneous quantification of esomeprazole,rabeprazole and levosulpiride in human plasma

A high throughput ultra pressure liquid chromatography-mass spectrometry （UPLC-MS/MS） method with good sensitivity and selectivity has been developed and validated for simultaneous quantification of esomeprazole, rabeprazole and levosulpiride in human plasma using lansoprazole as internal standard （IS）. The extraction method based on liquid-liquid extraction technique was used to extract the analytes and IS from of 50 μL of human plasma using methyl tert-butyl ether：ethyl acetate （80：20, v/v）, which offers a high recovery. Chromatographic separation of analytes and IS was achieved on a Hypersil gold C18 column using gradient mobile phase consisting of 2 mM ammonium formate/acetonitrile. The flow rate was set at 0.5 mL/min to elute all the analytes and IS within 1.00 min runtime. Detection of target compounds was performed on a triple quadruple mass spectrometer by multiple reaction monitoring （MRM） mode via positive electrospray ionization （ESI）. Method validation results demonstrated that the developed method has good precision and accuracy over the concentration ranges of 0.1-2000 ng/mL for each analyte. Stability of compounds was established in a battery of stability studies, i.e., bench top, autosampler, dry extract and long-term storage stability as well as freeze-thaw cycles. The validated method has been successfully applied to analyze human plasma samples for application in pharmaco- kinetic studies.

Pharmacokinetics of levosulpiride after single and multiple intramuscular administrations in healthy Chinese volunteers

The main purpose of this study was to evaluate the pharmacokinetics of levosulpiride in humans after single and multiple intramuscular injections.Six males and six females received single dose of either 25 mg or 50 mg levosulpiride,or multiple doses of 25 mg every 12 h for 5 consecutive days.In the single 25 mg study,the mean peak plasma concentration(C max)was 441 ng/mL,the mean area under the concentration–time curve from 0 to 36 h(AUC_(0–36))was 1724 ng h/mL,and the mean elimination half-life(t_(1/2))was 7.0 h.In the single 50 mg study,the mean C max was 823 ng/mL,the mean AUC_(0–36) was 3748 ng·h/mL,and the mean t_(1/2) was 6.8 h.After multiple doses of 25 mg levosulpiride,the average plasma concentration(C av)was 136 ng/mL,the fluctuation index(DF)was 3.60,and the accumulation ratio(R)was 1.2.Levosulpiride injections appeared to be well tolerated by the subjects,and can be used for successive administration.

Electrogastrography associated with symptomatic changes after prokinetic drug treatment for functional dyspepsia

AIM:To evaluate the effect of prokinetic drugs on electrogastrography(EGG) parameters according to symptomatic changes in patients with functional dyspepsia(FD).METHODS:Seventy-four patients with FD were prospectively enrolled in this study between December 2006 and December 2010.We surveyed the patients using a questionnaire on dyspeptic symptoms before and after an 8-wk course of prokinetic drug treatment.We also measured cutaneous pre-prandial and postprandial EGG recordings including percentage of gastric waves(normogastria,bradygastria,tachygastria),dominant frequency(DF),dominant power(DP),dominant frequency instability coefficient(DFIC),dominant power instability coefficient(DPIC),and the ratio of post-prandial to fasting in DP before and after the 8-wk course of prokinetic drug treatment.RESULTS:Fifty-two patients(70%) achieved symptomatic improvement after prokinetic drug treatment.Patients who had normal gastric slow waves showed symptom improvement group after treatment.Postprandial DF showed a downward trend in the symptom improvement group,especially in the itopride group.Post-prandial DP was increased regardless of symptom improvement,especially in the itopride group and mosapride group.Post-prandial DFIC and DPIC in the symptom improvement group were significantly increased after the treatment.The EGG power ratio was increased after treatment in the symptom improvement group(0.50 ± 0.70 vs 0.93 ± 1.77,P = 0.002),especially in the itopride and levosulpiride groups.CONCLUSION:Prokinetics could improve the symptoms of FD by regulating gastric myoelectrical activity,and EGG could be a useful tool in evaluating the effects of various prokinetics.