This paper describes a simple, rapid and sensitive liquid chromatography tandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope （duloxetine ds） was us...This paper describes a simple, rapid and sensitive liquid chromatography tandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope （duloxetine ds） was used as an internal standard. Analyte and the internal standard were extracted from 100 btL of human plasma via solid phase extraction technique using Oasis HLB cartridges. The chromatographic separation was achieved on a Cl8 column by using a mixture of acetonitrile 5 mM ammonium acetate buffer （83：17, v/v） as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear （r2≥0.99） over the concentration range of 0.05 101 ng/mL. Multiple-reaction monitoring mode （MRM） was used for quantification of ion transitions at rn/z 298.3/154.1 and 303.3/159.1 for the drug and the internal standard, respectively. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.展开更多
AIM: To investigate the diagnostic efficacy of 24-h and exertional esophageal pH-metry and manometry in patients with recurrent chest pain. METHODS: The study included 111 patients (54% male) with recurrent angina-lik...AIM: To investigate the diagnostic efficacy of 24-h and exertional esophageal pH-metry and manometry in patients with recurrent chest pain. METHODS: The study included 111 patients (54% male) with recurrent angina-like chest pain, non-respon- sive to therapy with proton pump inhibitors. Sixty-five (59%) had non-obstructive lesions in coronary artery angiography, and in 46 (41%) significant coronary artery narrowing was found. In all patients, 24-h esophageal pH-metry and manometry, and treadmill stress tests with simultaneous esophageal pH-metry and manometry monitoring were performed. During a 24-h examination the percentage of spontaneous chest pain (sCP) episodes associated with acid reflux or dysmotility (symptom index, SI) was calculated. Patients with SI > 50% for acid gastroesophageal reflux (GER) were classified as having GER-related sCP. The remaining symptomatic individuals were determined as having non-GER-related sCP. During the stress test, the occurrence of chest pain, episodes of esophageal acidification (pH < 4 for 10 s) and esophageal spasm with more than 55% of simultaneous contractions (exercise-provoked esophageal spasm or EPES) were noted. RESULTS: Sixty-eight (61%) individuals reported sCP during 24-h esophageal function monitoring. Eleven of these (16%) were classified as having GER-related sCP and 53/68 (84%) as having non-GER-related sCP. The exercise-provoked chest pain during a stress test occurred in 13/111 (12%) subjects. In order to compare the clinical usefulness of 24-h esophageal function monitoring and its examination limited only to the treadmill stress test, the standard parameters of diagnostic test evaluation were determined. The occurrence of GER- related or non-GER-related sCP was assumed as a "gold standard". Afterwards, accuracy, sensitivity and specificity were calculated. These parameters expressed a prediction of GER-related or non-GER-related sCP occurrence by the presence of chest pain, esophageal acidification and EPES. Accuracy, sensitivity and specificity of chest pain during the stress test predicting any sCP occurrence were 28%, 35% and 80%, respectively, predicting GER- related sCP were 42%, 0% and 83%, respectively, and predicting non-GER-related sCP were 57%, 36% and 83%, respectively. Similar values were obtained for exercise-related acidification with pH < 4 longer than 10 s in the prediction of GER-related sCP (44%, 36% and 92%, respectively) and EPES in relation to non-GER-related sCP (48%, 23% and 84%, respectively). CONCLUSION: The presence of chest pain, esophageal acidification and EPES had greater than 80% specificity to exclude the GER-related and non-GER-related causes of recurrent chest pain.展开更多
文摘This paper describes a simple, rapid and sensitive liquid chromatography tandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope （duloxetine ds） was used as an internal standard. Analyte and the internal standard were extracted from 100 btL of human plasma via solid phase extraction technique using Oasis HLB cartridges. The chromatographic separation was achieved on a Cl8 column by using a mixture of acetonitrile 5 mM ammonium acetate buffer （83：17, v/v） as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear （r2≥0.99） over the concentration range of 0.05 101 ng/mL. Multiple-reaction monitoring mode （MRM） was used for quantification of ion transitions at rn/z 298.3/154.1 and 303.3/159.1 for the drug and the internal standard, respectively. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.
基金Supported by Resources from the Nicolaus Copernicus University in Toruń for statutory activity in the Department of Gastroenterology, Vascular Diseases and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland
文摘AIM: To investigate the diagnostic efficacy of 24-h and exertional esophageal pH-metry and manometry in patients with recurrent chest pain. METHODS: The study included 111 patients (54% male) with recurrent angina-like chest pain, non-respon- sive to therapy with proton pump inhibitors. Sixty-five (59%) had non-obstructive lesions in coronary artery angiography, and in 46 (41%) significant coronary artery narrowing was found. In all patients, 24-h esophageal pH-metry and manometry, and treadmill stress tests with simultaneous esophageal pH-metry and manometry monitoring were performed. During a 24-h examination the percentage of spontaneous chest pain (sCP) episodes associated with acid reflux or dysmotility (symptom index, SI) was calculated. Patients with SI > 50% for acid gastroesophageal reflux (GER) were classified as having GER-related sCP. The remaining symptomatic individuals were determined as having non-GER-related sCP. During the stress test, the occurrence of chest pain, episodes of esophageal acidification (pH < 4 for 10 s) and esophageal spasm with more than 55% of simultaneous contractions (exercise-provoked esophageal spasm or EPES) were noted. RESULTS: Sixty-eight (61%) individuals reported sCP during 24-h esophageal function monitoring. Eleven of these (16%) were classified as having GER-related sCP and 53/68 (84%) as having non-GER-related sCP. The exercise-provoked chest pain during a stress test occurred in 13/111 (12%) subjects. In order to compare the clinical usefulness of 24-h esophageal function monitoring and its examination limited only to the treadmill stress test, the standard parameters of diagnostic test evaluation were determined. The occurrence of GER- related or non-GER-related sCP was assumed as a "gold standard". Afterwards, accuracy, sensitivity and specificity were calculated. These parameters expressed a prediction of GER-related or non-GER-related sCP occurrence by the presence of chest pain, esophageal acidification and EPES. Accuracy, sensitivity and specificity of chest pain during the stress test predicting any sCP occurrence were 28%, 35% and 80%, respectively, predicting GER- related sCP were 42%, 0% and 83%, respectively, and predicting non-GER-related sCP were 57%, 36% and 83%, respectively. Similar values were obtained for exercise-related acidification with pH < 4 longer than 10 s in the prediction of GER-related sCP (44%, 36% and 92%, respectively) and EPES in relation to non-GER-related sCP (48%, 23% and 84%, respectively). CONCLUSION: The presence of chest pain, esophageal acidification and EPES had greater than 80% specificity to exclude the GER-related and non-GER-related causes of recurrent chest pain.
