| The adverse events caused by intravenous infusion of traditional Chinese medicine injection happened frequently.The ingredients of Chinese medicine injection with more instability factors are complex and need to establish a simultaneous determination method for quality control of various active ingredients.With effective development of preparing solution in top three hospitals' PIVAS,traditional Chinese medicine injection lie in a pivotal position.To explore quality changes from configuration to infusion,the stability of Chinese medicine injection transfusions influenced by room light need to be studied.The aim was to guide clinical rational drug use and reduce the occurrence of adverse events.Kuhuang injection is made of Sophora flavescens,Rheum officinale,artemisia capillaris,Radix bupleuri and Radix pulsatillae.This pure traditional medicine injection can clear wet heat and yellow skin color as well as soothing the liver.Guhong injection is made of aceglutamide and extraction of Carthamus tinctorius.This Chinese-Western combination preparation can coordinate to protect ischemic damage,resistant chronic hypoxia,improve cognitive function.This study established a UPLC/MS/MS method to determine 7 active ingredients in kuhuang injection and 7 active ingredients in guhuang injection.Establish the stability study method of the three kinds of finished product infusion in kuhuang injection and four kinds of finished product infusion in guhong injection.This study can be fast,efficient,accurate for quality control and scientific,objective and accurate analysis of finished product infusion with the influence of room light.The results were reasonable,safe and effective for clinical drug use and provide significant reference basis.Part one Simultaneous determination of seven active components in kuhuang injectionObjective: To develop a UPLC-MS/MS method for the determination of matrine,sophocarpine,emodin,rhein,chlorogenic acid,sarkosaponin a,aloe-emodin in kuhuanng injection.Methods: Phenomenex Kinetex C18 column(50 mm×2.1 mm,5 ?m)was used and the temperature was set at 20 ?.The samples were eluted with methol and water containing 0.1% formic acid(v/v)in a gradient elution at a flow rate of 0.5 m L/min,and the injection volume was 5 ?L.Multiple-reaction monitoring(MRM)scanning was employed for quantification with switching electrospray ion source polarity in positive and negative mode with spray voltage of 5500 V and-4500 V.The turbo spray temperature was maintained at600 ?.The precursor-to-product ion paris of matrine,sophocarpine,emodin,rhein,chlorogenic acid,sarkosaponin a,aloe-emodin in kuhuang injection were 249.2/148.1,247.2/136.1,269.0/225.0,283.1/239.0,353.2/190.9,825.5/779.4,271.1/225.0 respectively.Results: The complete separation was obtained within 7 min for the seven compounds in kuhuang injection.The good linear relationships between peak areas and content of each compound were obtained(r?0.9973).The LOD and LOQ were below 1.528 and 3.055 ng/m L respectively.The intra-day precision RSD(%)ranged from 1.04~2.98(n=6)and inter-day precision RSD(%)ranged from 1.33~2.91(n=6)and stability within 12 h as well as repetition was good.The average recoveries of the compounds ranged from95.20% to 104.00%.Conclusions: The method is convenint and rapid with good repeatability and specifity which suitable for simultaneous determination for 7 ingredients in kuhuang injection for offering more overall quatity control accordings.Part Two Simultaneous determination of seven active components in guhong injectionObjective: To develop a UPLC-MS/MS method for the determination of aceglutamide,hydroxysafflower yellow A,kaempferide,kaempferol,quercetin,syringin,rutin in guhong injection.Methods: Phenomenex Kinetex C18 column(50 mm×2.1 mm,5 ?m)was used and the temperature was set at 20 ?.The samples were eluted with acetonitrile and water containing 0.1% formic acid(v/v)in a gradient elution at a flow rate of 0.5 m L/min,and the injection volume was 5 ?L.Multiple-reaction monitoring(MRM)scanning was employed for quantification with switching electrospray ion source polarity in positive and negative mode with spray voltage of 5500 V and-4500 V.The turbo spray temperature was maintained at 600 ?.The precursor-to-product ion paris of aceglutamide,hydroxysafflower yellow A,kaempferide,kaempferol,quercetin,rutin,syringin in guhong injection were 453.1/351.2,423.1/367.0,301.0/150.9,315.1/300.0,284.9/93.0,439.0/383.0,325.0/163.1 respectively.Results: The complete separation was obtained within 7 min for the seven compounds in guhong injection.The good linear relationships between peak areas and content of each compound were obtained(r?0.9988).The LOD and LOQ were below 0.18 and 0.6 ng/m L respectively.The intra-day precision RSD(%)ranged from 1.45~3.81(n=6)and inter-day precision RSD(%)ranged from 0.81~3.67(n=6)and stability within 12 h as well as repetition was good.The average recoveries of the compounds ranged from95.30% to 104.10%.Conclusions: The method is convenint and rapid with good repeatability and specifity which suitable for simultaneous determination for 7 ingredients in guhong injection for offering more overall quatity control accordings.Part Three Stability study of kuhuang injection compatibility solutionsObjective: To investigate compatible stability and light's influence of kuhuang injection with 5% glucose injection,10% glucose injection,fructose injection within 48 hours at room temperature with low or high content.Methods: Taking kuhuang injection with 3 solutions at room temperature,according to high or low dose,study the compatible stability of solution with changes of appearance,particulates,p H,contents of matrine and sophocarpine.The appearance and particulates were determined according to characteristics examination method in China pharmacopoeia of 2015.The contents of matrineand sophocarpine were determined by HPLC-UV method.Results: The kuhuang injection compatibility solution showed no change of appearance of deep yellow clear solution within 48 hours.The p H of 10%glucose injection transfusion increased extremly at 6 h in low concentration group exposed to room light,which stable than the group protect fom light.The particulates fit regulation.The kuhuang injection compatibility solution of fructose injection showed the particulates did not fit regulation that others did and showed a little acidity of p H value in high concentration group.The contents of matrine showed no change and the content of sophocarpine decreased in each group and the group protect from light showed stable than another.Conclusions: The fructose injection did not suit the solvent of kuhuang injection.Each transfusion showed stable if protected from light whenever.It had better use transfusions as early as possible to reduce the degradation of some effect componets.Part Four Stability study of guhong injection compatibility solutionsObjective: To develop a method for simultaneously determining aceglutamide,hydroxysafflower A,syringin,adenosine in guhong injection.To investigate compatible stability and light's influence of Guhong Injection with5% glucose injection,10% glucose injection,0.9% NaCl injection,fructose injection within 48 hours at room temperature with common dose as well as the reasonability of overdose in ICU.Methods: Using HPLC-UV method and taking guhong injection with 4solutions at room temperature,according to high or low dose,study the compatible stability of solution with changes of appearance,p H,particulates,contents of 4 componets.Results: The common dose of guhong injection compatibility solution showed no change of appearance of deep yellow clear solution within 48 hours.The compatibility solution of 0.9% NaCl injection showed the particulates did not fit regulation that others did(n=3).The compatibility solution of fructose injection showed decrease of componets.The groupprotected from light showed stability than the other.The overdose compatibility solution in ICU showed the particulates did not fit regulation and componets decreased.Conclusions: The common dose of guhong injection with 0.9% NaCl injection should be used after 1 hour.The fructose injection did not be recommended.The process of storage and infusion should be protected from light.The overdose of compatibility solution in ICU should not be recommended. |
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