Nanjing Clinical Technology Laboratories Inc.

Nanjing, China

Nanjing Clinical Technology Laboratories Inc.

Nanjing, China
SEARCH FILTERS
Time filter
Source Type

Li Q.,China Pharmaceutical University | Wang Y.,Nanjing Clinical Technology Laboratories Inc. | Liu L.,China Pharmaceutical University | Ma P.,Peking Union Medical College | And 2 more authors.
European Journal of Drug Metabolism and Pharmacokinetics | Year: 2016

Background and Objectives: Roflumilast is a selective, oral phosphodiesterase 4 inhibitor approved for the treatment of severe chronic obstructive pulmonary disease. The aim of this study was to evaluate the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy Chinese subjects, and the effects of gender and food on their respective pharmacokinetic profiles. Methods: 36 healthy Chinese subjects were recruited in a randomized, single-center, open-label, parallel group study and assigned to 0.25-, 0.375-, and 0.5-mg dose groups. The single-dose pharmacokinetic studies in fasting condition were carried out in all groups. Moreover, the food effect study and multiple-dose study were conducted in 0.375-mg dose group. Serial blood samples were collected over 168 h after dosing, and plasma concentrations of roflumilast and roflumilast N-oxide were determined using a validated LC-MS/MS method. Results: After oral administration of single doses of 0.25, 0.375 and 0.5 mg of roflumilast under fasting condition, the mean AUC0–72h for roflumilast was 21.7 ± 8.3, 29.8 ± 8.3 and 54.2 ± 21.3 ng·h/mL, respectively. Meanwhile the mean AUC0–168h for roflumilast N-oxide was 290 ± 103, 385 ± 107 and 673 ± 245 ng·h/mL, respectively. In the steady state after the multi-dose administration, the exposure to roflumilast in the subjects increased 20–40 %, and the exposure to roflumilast N-oxide increased about 169 %, compared to the single-dose administration. No statistically significant effect of gender on the disposition of roflumilast and roflumilast N-oxide was observed. Food had no effect on systemic exposure to roflumilast and roflumilast N-oxide in the subjects, but delayed the Tmax of roflumilast by 0.9 h and reduced the Cmax of roflumilast by approximately 20 %. Conclusion: Based upon between-study comparison, peak and systemic exposure of roflumilast and roflumilast N-oxide were higher in Chinese than that in Caucasian subjects after oral administration of the same dose (i.e., 0.25 and 0.5 mg). It implies that the therapeutic dose for Chinese patients may be different from that for Caucasians, warranting further investigation. © 2016 Springer International Publishing Switzerland


Liu R.,China Pharmaceutical University | Liu R.,Nanjing Clinical Technology Laboratories Inc. | Wu Y.,China Pharmaceutical University | Wu Y.,Nanjing Clinical Technology Laboratories Inc. | And 9 more authors.
RSC Advances | Year: 2015

Shuanghua Baihe tablets (SBT) are a traditional Chinese medicine formula which is used for treatment of oral mucositis (OM) for more than 30 years in China. So far, there has been no report of the quantification of the major components in SBT and their pharmacokinetics in humans. In this study, high performance liquid chromatography coupled to triple-quadrupole mass spectrometry was used to determine the content of the major compounds in SBT and to evaluate the pharmacokinetics of nine major constituents (berberine, epiberberine, coptisine, palmatine, jatrorrhizine, magnoflorine, berberrubine, corynoline and acetylcorynoline) following single and multiple oral administrations of SBT in healthy subjects. This study was an open-label and 2-period clinical trial. It was conducted in 12 Chinese healthy subjects. Each subject received a single dose in period 1 and multiple doses in period 2. Blood samples were collected and determined over 96 h. Subjects underwent safety assessments and were monitored for adverse events. There was no serious adverse event, death or withdrawal. Gender had a significant effect on the pharmacokinetics of the active alkaloids except for magnoflorine, berberrubine, corynoline and acetylcorynoline. Compared with the single dosing, the exposure of the alkaloids increased significantly except for berberrubine after multiple dosing. Single and multiple oral doses of SBT were safe in healthy Chinese subjects. The accumulation of the alkaloids to different extents was observed with repeated dosing except for berberrubine. This work provides useful information for clinical application in the treatment of OM, and a scientific basis for the study on the material foundation of the medicinal effectiveness of SBT and its mechanism of action. © The Royal Society of Chemistry.


Liu R.,China Pharmaceutical University | Liu R.,Nanjing Clinical Technology Laboratories Inc. | Zheng L.,National Key Institute of Traditional Chinese Medicine Quality Control | Cheng M.,China Pharmaceutical University | And 9 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2016

Corynoline and acetycorynoline, the major active components derived from Corydalis bungeana Herba, showed multiple pharmacological activities. However, quantification of the two compounds in human urine has not been reported. A simple liquid chromatography with tandem mass spectrometry method for the simultaneous determination of corynoline and acetycorynoline in human urine has been developed and fully validated. The analytes were extracted from urine samples by simple liquid-liquid extraction. Chromatographic separation was achieved on a Hedera ODS-2C18 column with the mobile phase of water (containing 0.5% formic acid) and acetonitrile (28:72, v/v) at a flow rate of 0.4 mL/min. A tandem mass spectrometric detection was conducted using multiple reaction monitoring via an electrospray ionization source in positive mode. The monitored ion transitions were m/z 368.1 → 289.1 for corynoline, m/z 410.2 → 289.2 for acetycorynoline and m/z 380.2 → 243.2 for donepezil (internal standard), respectively. The calibration curves were linear (correlation coefficients > 0.9970) over the concentration ranges of 3.0-3000 pg/mL for corynoline and 3.0-1000 pg/mL for acetycorynoline. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 3.0 pg/mL for both analytes. The intra- and inter-day precision was lower than 10% in terms of relative standard deviation for the low, medium, and high quality control samples, and lower than 16% for the LLOQ samples of the analytes. The accuracy was within ±10% in terms of relative error for both analytes. The method was successfully applied to a urinary excretion study after oral administration of the Chinese medicine formula Shuanghua Baihe tablets in healthy volunteers. The urinary excretion profiles of corynoline and acetycorynoline in human were first reported. The results of this study suggest that renal excretion was not the main excretion pathway of corynoline and acetycorynoline in humans. © 2016 Elsevier B.V.


Cheng M.,China Pharmaceutical University | Cheng M.,Nanjing Clinical Technology Laboratories Inc. | Liu R.,China Pharmaceutical University | Liu R.,Nanjing Clinical Technology Laboratories Inc. | And 9 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2016

An LC-MS/MS method was developed and validated for the simultaneous determination of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine in human urine. The sample preparation procedure involved the four-fold dilution of the urine samples with acetonitrile/water (1:3, v/v). The chromatographic separation was achieved on a Hedera ODS-2 column under gradient elution at a flow rate of 0.4. mL/min with acetonitrile and water containing 0.5% formic acid as the mobile phase. The mass detection was performed in the positive mode. Calibration curves of the seven alkaloids showed good linearity (correlation coefficients. >. 0.9973) over their concentration ranges. To meet the requirements of urinary excretion study for each alkaloid in human, the lower limit of quantification was set at different values from 0.05063. ng/mL to 2.034. ng/mL for the seven alkaloids, respectively. The intra- and inter-batch precision and accuracy were all within ±15%. No matrix effect was observed for the analytes. The validated method was applied to the excretion study for the seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets. The average 72. h cumulative urinary excretion of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine accounted for 1.81%, 0.27%, 0.29%, 0.046%, 0.027%, 0.010% and 0.021% of the respective administered dose. © 2015 Elsevier B.V.


Gu P.,China Pharmaceutical University | Gu P.,Nanjing Clinical Technology laboratories Inc. | Liu R.-J.,China Pharmaceutical University | Liu R.-J.,Nanjing Clinical Technology laboratories Inc. | And 9 more authors.
Chinese Journal of Natural Medicines | Year: 2016

An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid (CGA) and taurocholic acid (TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatographic separation was achieved on a Hedera ODS-2 column with a gradient elution using 10 mmol·L-1 of ammonium acetate buffer solution containing 0.5% of formic acid - acetonitrile as mobile phase at a flow rate of 300 μL·min-1. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration ranges of 0.1-10 ng·mL-1 for CGA and 2-150 ng·mL-1 for TCA. It was successfully applied to a pharmacokinetic study of CGA and TCA in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets (SBTs). In the single-dose study, the maximum plasma concentration (Cmax), time to reach Cmax (Tmax) and elimination half-life (t1/2) of CGA were (0.763 8 ± 0.542 0) ng·mL-1, (1.0 ± 0.5) h, and (1.3 ± 0.6) h, respectively. In the multiple-dose study, the Cmax, Tmax and t1/2 of CGA were (0.663 7 ± 0.583 3) ng·mL-1, (1.1 ± 0.5) h, and (1.4 ± 0.7) h, respectively. For TCA, no significant characteristic increasing plasma TCA concentration-time curve was found in the volunteers after oral administration of SBTs, indicating its complicated process in vivo as an endogenous ingredient. © 2016 China Pharmaceutical University.


Wu Y.,China Pharmaceutical University | Wu Y.,Nanjing Clinical Technology Laboratories Inc. | Liu R.,China Pharmaceutical University | Liu R.,Nanjing Clinical Technology Laboratories Inc. | And 9 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2015

Shuanghua Baihe tablets (SBT) is a traditional Chinese medicinal formula which has been used to treat recurrent aphthous stomatitis for many years. To study the pharmacokinetic profiles of berberine, epiberberine, coptisine, palmatine, jatrorrhizine, magnoflorine, berberrubine, corynoline and acetylcorynoline in human after administration of SBT, a sensitive liquid chromatography-tandem mass spectrometry method was developed and fully validated for the simultaneous quantification of these nine alkaloids in human plasma. After protein precipitation, the nine alkaloids in human plasma sample was separated on a Hanbon C18 (150. mm. ×. 2.1. mm, 5. μm) column with gradient elution using methanol and 0.5% formic acid water solution, and detected by a triple quadrupole mass spectrometer with an electrospray ionization source. It is a challenge to design different calibration ranges for different analytes in a bioanalytical method for simultaneous determination of multi-analytes in bio-samples. To ensure that each alkaloid in the plasma was determined accurately by the simultaneous quantitation method, the upper limits of quantification for the nine alkaloids were designed at 100, 300, 800, 1800 and 5000. pg/mL, respectively, according to the maximum plasma concentration value of each alkaloid obtained from the pilot pharmacokinetic study. The lower limit of quantification was 15. pg/mL for berberine, epiberberine, coptisine, magnoflorine, berberrubine, corynoline and acetylcorynoline, while for palmatine and jatrorrhizine it was 1.5. pg/mL. This method was successfully applied to investigate the pharmacokinetic profiles of the nine alkaloids in healthy Chinese volunteers after a single oral administration of SBT. © 2015 Published by Elsevier B.V.


PubMed | Peking Union Medical College, Nanjing Clinical Technology Laboratories Inc. and China Pharmaceutical University
Type: | Journal: European journal of drug metabolism and pharmacokinetics | Year: 2016

Roflumilast is a selective, oral phosphodiesterase 4 inhibitor approved for the treatment of severe chronic obstructive pulmonary disease. The aim of this study was to evaluate the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy Chinese subjects, and the effects of gender and food on their respective pharmacokinetic profiles.36 healthy Chinese subjects were recruited in a randomized, single-center, open-label, parallel group study and assigned to 0.25-, 0.375-, and 0.5-mg dose groups. The single-dose pharmacokinetic studies in fasting condition were carried out in all groups. Moreover, the food effect study and multiple-dose study were conducted in 0.375-mg dose group. Serial blood samples were collected over 168h after dosing, and plasma concentrations of roflumilast and roflumilast N-oxide were determined using a validated LC-MS/MS method.After oral administration of single doses of 0.25, 0.375 and 0.5mg of roflumilast under fasting condition, the mean AUCBased upon between-study comparison, peak and systemic exposure of roflumilast and roflumilast N-oxide were higher in Chinese than that in Caucasian subjects after oral administration of the same dose (i.e., 0.25 and 0.5mg). It implies that the therapeutic dose for Chinese patients may be different from that for Caucasians, warranting further investigation.


Liu D.,China Pharmaceutical University | Liu D.,Nanjing Clinical Technology Laboratories Inc. | Geng T.,China Pharmaceutical University | Geng T.,Nanjing Clinical Technology Laboratories Inc. | And 3 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2016

A selective and reproducible HPLC–MS/MS method was developed and fully validated for the determination of cefbuperazone in human plasma and urine. Samples were prepared using protein precipitation and separated on a Zorbax Eclipse Plus C18 column (2.1 × 50 mm, 3.5 μm). The API-4000 mass spectrometer was operated under multiple reaction monitoring mode (MRM) using the electrospray ionization technique. Linearity was achieved from 0.250 to 250 μg/mL in plasma and 20.0–5000 μg/mL in urine. The method was successfully applied to a pharmacokinetic study of cefbuperazone in healthy Chinese volunteers after drip intravenous infusion of 0.5, 1.0, 2.0 g cefbuperazone sodium injection. Cefbuperazone reached a maximum concentration (Cmax) of 44.7 ± 8.1 μg/mL, 86.7 ± 12.7 μg/mL and 168 ± 14 μg/mL in 0.5, 1.0 and 2.0 g dose groups respectively, at 60 min after the start of infusion. The half-life (t1/2) was between 1.8–1.9 h, and the elimination constant (kel) was between 0.36–0.39 h−1. The results proved that cefbuperazone showed linear pharmacokinetic profile in the dose range of 0.5–2.0 g without gender difference. Drug accumulation was not observed. Cefbuperazone reached the maximum excretion rate in urine 2 h after the start of infusion. About 60.0% of the administered drug was excreted via urine as unchanged form within 12 h. The cumulative excretion of cefbuperazone after single drip intravenous infusion was proportional to the administered dose within the range from 0.5 g to 2.0 g. © 2016 Elsevier B.V.


Liu R.,China Pharmaceutical University | Liu R.,Nanjing Clinical Technology Laboratories Inc. | Gu P.,China Pharmaceutical University | Gu P.,Nanjing Clinical Technology Laboratories Inc. | And 10 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2016

Corynoline, the major isoquinoline alkaloid component derived from Corydalis bungeana Herba, has greatly impressed many scientists due to its various pharmacological effects. However, there is little information on its pharmacokinetics. In this study, a sensitive and rapid liquid chromatography with tandem mass spectrometry method has been developed and validated for the determination of corynoline in rat plasma. The calibration curve showed good linearity within the concentration range of 0.01-20ng/mL. The method was fully validated and successfully applied in a pharmacokinetic study of corynoline in rats, in which the rats were treated with corynoline, corynoline combined with berberine and the traditional Chinese medicine formula Shuanghua Baihe tablets (SBT, containing corynoline, berberine and other ingredients), respectively. Corynoline showed low bioavailability and a high elimination rate. The terminal elimination half-life was prolonged about 3-fold, and the maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC0-12) of corynoline were increased by 46.5% and 34.2%, respectively, when the same dosage of corynoline was administered in SBT. Furthermore, compared with the corynoline group, the Cmax and AUC0-12 were increased by 11.1-fold and 5.0-fold respectively, in the rats treated with corynoline combined with berberine. The results suggested that oral administration of the SBT prolonged the elimination half-life of corynoline and increased its bioavailability. Berberine played an important role in the pharmacokinetic drug-drug interaction of corynoline and ingredients in SBT, and the influence of other co-existing compounds in SBT on the pharmacokinetic profiles of corynoline could not be ignored. © 2015 Elsevier B.V.

Loading Nanjing Clinical Technology Laboratories Inc. collaborators
Loading Nanjing Clinical Technology Laboratories Inc. collaborators