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This study provided a novel and generally applicable method to determine ziyuglycoside I and ziyuglycoside II in rat plasma based on liquid chromatography with tandem mass spectrometry. A single step of liquid-liquid extraction with n-butanol was utilized, and ginsenoside Rg3 was chosen as internal standard. Final extracts were analyzed based on liquid chromatography with tandem mass spectrometry. Chromatographic separation was achieved using a Thermo Golden C18 column, and the applied gradient elution program allowed for the simultaneous determination of two ziyuglycosides in a one-step chromatographic separation with a total run time of 10 min. The fully validated methodology for both analytes demonstrated high sensitivity (the lower limit of quantitation was 2.0 ng/mL), good accuracy (% RE ≤ ± 15) and precision (% RSD ≤ 15). The average recoveries of both ziyuglycosides and internal standard were all above 75% and no obvious matrix effect was found. This method was then successfully applied to the preclinical pharmacokinetic studies of ziyuglycoside I and ziyuglycoside II. The presently developed methodology would be useful for the preclinical and clinical pharmacokinetic studies for ziyuglycoside I and ziyuglycoside II. [ABSTRACT FROM AUTHOR]

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) has received considerable attention in recent years since it allows molecular mapping of diverse bimolecular in animal/plant tissue sections, although some barriers still exist in absolute pixel-to-pixel quantification. Octreotide, a synthetic somatostatin analogue, has been widely used to prevent gastrointestine bleeding in the clinic. The aim of the present study is to develop a MALDI-TOF-MSI method for quantitatively visualizing spatial distribution of octreotide in mouse tissues. In this process, a structurally similar internal standard was spotted onto tissue section together with matrix solution to minimize signal variation and give excellent quantitative results. The 2,5-dihydroxybenzoic acid was chosen as the most suitable matrix via comparing the signal/noise generated by MALDI-TOF-MSI after cocrystallization of octreotide with different matrix candidates. The reliability of MALDI-TOF-MSI, with respect to linearity, sensitivity and precision, was tested via measuring octreotide in fresh tissue slices at different concentrations. The validated method was then successfully applied to visualize the distribution of octreotide in mouse tissues after oral administration of octreotide at 20 mg/kg. The results demonstrated that MALDI-TOF-MSI could not only clearly visualize the spatial distribution of octreotide, but also make the calculation of the key pharmacokinetic parameters (T max and t 1/2 ) possible. More importantly, the tissue concentration-time curves of octreotide determined by MALDI-TOF-MSI agreed well with those measured based on LC–MS/MS.These findings illustrate the potential of MALDI-TOF-MSI in pharmacokinetic profiling during drug development. [ABSTRACT FROM AUTHOR]

Application of imaging mass spectrometry in drug pharmacokinetics remains challenging due to its weak quantitative capability. Herein, an imaging mass microscope (iMScope), equipped with an optical microscope, an atmospheric pressure ion-source chamber for matrix-assisted laser desorption/ionization (AP-MALDI) and a hybrid quadrupole ion trap time-of-flight (QIT-TOF) analyzer, was first validated and applied to visualize drug disposition in vivo . The distribution and elimination rate of the therapeutic peptide octreotide, a long-acting analogue of the natural hormone somatostatin, was first calculated based on the data determined by iMScope system combining a novel relative exposure strategy. Microspotted pixel-to-pixel quantitative iMScope provided a relative amount of octreotide presented in a thin stomach/intestinal section while preserving its original spatial distribution. The images of dosed mouse stomach clearly demonstrated the transport process of octreotide from the mucosal layer to the muscle side. More importantly, octreotide was found to eliminate from the intestines rapidly, the absorption peak time (T max ) appeared at 40 min and the half-life time (t 1/2 ) was calculated as 37.7 min according to the elimination curves. Comparisons to the LC-MS/MS data adequately indicated that the quantification approach and methodology based on the iMScope was reliable and practicable for drug pharmacokinetic study. [ABSTRACT FROM AUTHOR]

In this contribution, the metabolic and pharmacokinetic characteristics for the therapeutic peptide HM-3 were investigated using LC-Q-TOF/MS and LC–MS/MS systems combing a fast biological sample processing method. According to the accurate MS 1 and MS 2 data generated by LC-Q-TOF/MS, a total of 6 metabolites in rats were detected and tentatively identified as the degradation products which formed by successive loss of amino acid from HM-3. The structures of the 2 main metabolites (M1 and M2) were confirmed by comparing the chromatographic and mass spectrographic characteristics with the corresponding synthetic standards. Then, an absolute quantitative analysis method based on LC–MS/MS system was built and fully validated with respect to linearity, sensitivity, accuracy, precision, matrix effect, stability, etc . The results indicated that HM-3, M1 and M2 were linear in peak area ratios over the concentration range of 0.5–200.0 ng/mL with a correlation coefficient > 0.99. The intra-day and inter-day precisions (RSD%) were less than 15%, and the accuracy was below 10% in terms of RE%. The validated method was then successfully applied to the studies of preclinical pharmacokinetics for HM-3. [ABSTRACT FROM AUTHOR]

Pidotimod, ( R )-3-[( S )-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, was frequently used to treat children with recurrent respiratory infections. Preclinical pharmacokinetics of pidotimod was still rarely reported to date. Herein, a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated to determine pidotimod in rat plasma, tissue homogenate and Caco-2 cells. In this process, phenacetin was chosen as the internal standard due to its similarity in chromatographic and mass spectrographic characteristics with pidotimod. The plasma calibration curves were established within the concentration range of 0.01–10.00 μg/mL, and similar linear curves were built using tissue homogenate and Caco-2 cells. The calibration curves for all biological samples showed good linearity (r > 0.99) over the concentration ranges tested. The intra- and inter-day precision (RSD, %) values were below 15% and accuracy (RE, %) was ranged from −15% to 15% at all quality control levels. For plasma, tissue homogenate and Caco-2 cells, no obvious matrix effect was found, and the average recoveries were all above 75%. Thus, the method demonstrated excellent accuracy, precision and robustness for high throughput applications, and was then successfully applied to the studies of absorption in rat plasma, distribution in rat tissues and intracellular uptake characteristics in Caco-2 cells for pidotimod. [ABSTRACT FROM AUTHOR]

Notoginsenosides, the main active gradients of Chinese traditional medicine Panax notoginseng, possesses a variety of biological activities including antioxidant property, anti-hyperglycemic, anti-obese, etc . However, pharmacokinetic evaluation for notoginsenosides is still a formidable task due to their low concentrations and complex components in vivo . The summation of this work generated a rapid and sensitive method for quantitative analysis of multi-notoginsenoside in rat plasma based on ultra fast liquid chromatographic-tandem mass spectrometric. After liquid–liquid extraction by n -butanol, notoginsenoside R1, Rg3, Rd, Rg2, Rb2, Rf, Rg1, Rb1 and Re were simultaneously monitored in negative ionization mode after separating on a Thermo ODS C 18 column (5 mm 50 mm × 2.1 mm) by a binary gradient elution, and all compounds were analyzed within 9 min. Multiple reaction monitoring (MRM) was performed as follows: R1 ( m / z 967.7 → 637.4), Rg3 ( m / z 819.6 → 621.4), Rd ( m/z 981.6 → 783.5), Rg2 ( m / z 819.6 → 475.4), Rb2 ( m / z 1113.4 → 783.4), Rf ( m / z 835.6 → 475.4), Rg1 ( m / z 835.6 → 637.6), Rb1 ( m / z 1143.7 → 945.6), Re ( m / z 981.6 → 637.4), internal standard (digoxin, m / z 815.5 → 779.4). Validation parameters (linearity, sensitivity, intra-and inter-assay precision and accuracy, recovery and matrix effect) were within acceptable ranges and biological extracts were stable during the entire storing and preparing process. This UFLC–MS/MS approach was further validated by being applied to the pharmacokinetic study for P. Notoginseng extract in rats, and the pharmacokinetic parameters were calculated by Winolin software. Thus, the presently developed methodology was simple, robust, accurate, precise, and would be useful for the pharmacokinetic studies for all kinds of notoginsenosides and other herbal saponins. [ABSTRACT FROM AUTHOR]