Studies On LC-MS/MS Method Of Anticancer Drugs And Interactions Between Xiaoaiping Injection And Anticancer Drugs

Malignancy is the tendency of a medical condition, especially tumors, to becomeprogressively worse and to potentially result in death, and chemotherapy is the primarymeans of treatment. Even if more selective therapies are developed, treatment schemeswill continue to be associated with classical cytotoxic agents. But cytotoxic agents cankill or inhibit not only tumor cells but also normal cells, and they usually lead to adversereactions (ADR) in the efficacy dose. These serious side effects will limit theireffectiveness. So therapeutic drug monitoring (TDM) is required to ensure the clinicaldose, monitor the individual treatment, and to increase efficacy and patients’compliance,reduce toxicity and pharmacokinetic differences, which will not produce serious toxicadverse effects.A sensitive, specific and selective liquid chromatography-tandem mass spectrometrymethod for the simultaneous determination of paclitaxel, docetaxel, vinblastine,vinorelbine, cyclophosphamide, ifosfamide, irinotecan, etoposide, gemcitabine,Carboplatin and pemetrexed, which were commonly used anticancer drugs, wasdeveloped and validated in human plasma for the first time. Liquid chromatography bycombining two kinds of extraction method, including the combination of0.1%formicacid and10mM ammonium acetate as aqueous phase and an Atlantis T3-C18column(2.1mm100mm I.D.，3μm，Waters，Ireland) using gradient elution, was optimized toresolve all interferences and enable reliable detection. In addition to the good massaccuracy achieved, tandem mass spectrometric and co-chromatography experimentsfurther confirmed the identity of the compounds. The assay was linear for all analyteswith correlation coefficients0.99. The mean recovery of all the analytes ranged from56.2to98.9%. The intra-and inter-day precision (%RSD) was within0.110.4%and0.112.3%. The analytical method was successfully applied to clinical samples fromcancer patients.The cytotoxic drugs mentioned above are also commonly used anticancer drugs inour hospital. So the sampling programs were worked out. Then the collected plasmasamples were measured and analyzed by this HPLC-MS/MS method. The results showthat this method is high specificity and sensitivity, simple operation, and high-throughputanalysis of biological samples, which can be widely used of the above drugs in TDM.The mostly cancer regimen is multi-drug combination therapy, and combined withtraditional Chinese preparations can improve efficacy and reduce toxicity. The stem of Marsdenia tenacissima (Roxb.) Wigh, commonly named as “Tong-Guan-Teng” or“Wu-Gu-Teng”, has long been used as a remedy to treat cancer in China. The extract ofMarsdenia tenacissima,(trade name: Xiao-Ai-Ping Injection (XAP), has uniquepharmacological mechanism of anti-tumor, which has high efficiency and low toxicity,and also can be anti-inflammatory, anti-asthmatic and diuretic. XAP has shown to beclinically in treatment of NSCLC (non-small cell lung cancer) when combined withchemotherapy almostly be combined with chemotherapy drugs (eg. paclitaxel anddocetaxel).The metabolism of docetaxel by human liver microsomes was investigated in vitro.The inhibitory effect of docetaxel on P450enzymes (CYP2C9, CYP2C19, CYP2D6,CYP3A4, and CYP2E1) was tested. The results showed that docetaxel had a stronginhibitory effect on CYP3A4, and the IC50value was0.34μM. Besides, XAP was thespecific substrate of CYP3A4. Considering the pharmacokinetics studies of XAP,docetaxel and the combination of both, the absorption and metabolism of docetaxelcould be inhibited after XAP and docetaxel administered orally to rats, owing to theinhibitory effect of XAP on CYP3A4.