Inhibitory effects of gemcitabine hydrochloride combined with ferroptosis inducers on the proliferation of PANC-1 cells / 药学实践杂志

Objective To study the effects of three ferroptosis inducers Erastin (Era), sulfasalazine (SASP) and artesunate (Art) alone or combined with gemcitabine hydrochloride (hcGEM) on the proliferation inhibition of Human pancreatic cell line PANC -1. Methods The CCK-8 method was used to detect the inhibitory effects of different concentrations of Era, SASP and Art alone or combined with hcGEM on the proliferation of PANC-1, and the combination index (CI) was used to judge whether three ferroptosis inducers combined with hcGEM had synergistic inhibitory effect on PANC-1. Results The three ferroptosis inducers and hcGEM alone or in combination could significantly inhibit the activity of PANC-1. The inhibitory effects were enhanced with the concentration increasing. The CI values of hcGEM-Era 4∶1 or 1∶4 combination group and hcGEM-SASP 1∶400 combination group were less than 1.The CI values of hcGEM-Art 1∶4 or 1∶16 combination group were less than 1 only within a certain concentration range. Conclusion The inhibitory effects of the three ferroptosis inducers and hcGEM alone or in combination were dose-dependent. The combination of hcGEM and three ferroptosis inducers could synergistically inhibit the proliferation of PANC-1.

Gemcitabine hydrochloride thermosensitive gel injection preparation and contents determination / 药学实践杂志

Objective To prepare gemcitabine hydrochloride thermosensitive gel injection and to stablish the determina‐tion methods of its contents .Methods Gemcitabine hydrochloride thermosensitive gel injection was prepared using PLGA‐PEG‐PLGA as thermosensitive viecle .The contents of gemcitabine hydrochloride were determined by HPLC .Results The formulation contained 40 mg/ml gemcitabine and 20% (wt) PLGA‐PEG‐PLGA with phase‐transition temperature of (37 ± 0 .15) ℃ ,showing the best viscosity around human body temperature .Gemcitabine hydrochloride presented a good linearity in the range of 5‐500 μg/ml(r=0 .999 8) ,which had good precision and reproducibility .The recovery rate of low ,middle and high concentrations of gemcitabine hydrochloride were (99 .5 ± 3 .2)% ,(100 .4 ± 2 .4)% ,(102 .1 ± 2 .4)% ,n=3 ,respectively . The average contents of gemcitabine hydrochloride in three batches of sample were (101 .87 ± 2 .95)% ,(99 .4 ± 2 .73)% , (98 .98 ± 0 .71)% ,n=3 ,respectively .Conclusion The quality of gemcitabine hydrochloride thermosensitive gel injection with PLGA‐PEG‐PLGA as matrix could be controlled .It is a promising new drug for pancreatic cancer .

Determination of related substances of gemcitabine hydrochloride by HPLC and study on its stability / 中国药学杂志

OBJECTIVE: To establish an HPLC method to determine the related substances of gemcitabine hydrochloride for quality control and observe the stability of gemcitabine hydrochloride. METHODS: An HPLC method was used to detect the related substances in gemcitabine hydrochloride. The stability of gemcitabine hydrochloride under various degradation conditions and the stability of its solution at room temperature were studied. RESULTS :Impurity Z2 was the main substance detected under each degradation conditions, the amount of Z2 increased proportionally with time at room temperature, and the increased amount exceeded the upper limit of quality standard by 20%(0.02%) at 24 h. CONCLUSION: Impurity Z2 markly increases under some degradation conditions and at room temperature, indicating that gemcitabine hydrochloride solution is unstable. The HPLC method has good specificity and linearity, which is suitable for quality control of gemcitabine hydrochloride and its pharmaceutical preparations.

Identification of major impurity in gemcitabine hydrochloride for injection by HPLC-QTOF / 中国药学杂志

OBJECTIVE: To elucidate the structure of the major impurity in gemcitabine hydrochloride for injection. METHODS: HPLC-QTOF-MS was adopted to analyze the structure of this impurity based on the fragmentation behavior of gemcitabine and this impurity. The separation was performed on a ZORBAX Eclipse XDB-C18(4.6 mm×250 mm, 5 μm) column. A mixture of 10% methanol and 90% 10 mmol·L-1 ammonium acetate(pH 5.7) was used as mobile phase. Flow rate was 1.0 mL·min-1. MS was performed under positive mode with 4.0 kV capillary voltage, 65 V skimmer, 310 kPa spray pressure, 11 L·min-1 drying gas (nitrogen) flow rate, 350°C drying gas temperature and 150 V fragmentor. CONCLUSION: This study offers scientific data for studying the origin of the impurity of gemcitabine hydrochloride and improving its quality.

Determination of Entrapment Efficiency of Gemcitabine Hydrochloride Liposome / 中国药房

OBJECTIVE: To establish a method for determining the entrapment efficiency of gemcitabine hydrochloride liposomes(GHL).METHODS: The liposome and the free gemcitabine hydrochloride were separated by ultrafiltration,and the content of free gemcitabine hydrochloride was determined by HPLC.The entrapment efficiency of gemcitabine hydrochloride liposomes was computed as well.RESULTS: The recovery rate in ultrafiltration methods was 97.8%～100.1% for blank substance versus 99.0%～100.1% for sample.The linear range of gemcitabine hydrochloride was 1.0～80.0 mg?L-1(r=0.999 3) and its average recovery rate was 98.7～101.2%,and its inter-day and intra-day RSD were all less than 3% and its average entrapment efficiency was 81.21%.CONCLUSION: The method is simple,accurate and applicable for the determination of the entrapment efficiency of gemcitabine hydrochloride liposomes.