In situ analysis of drugs has been in increasing demand in many fields. As an updated version of capillary-in-capillary electrospray ionization (CC-ESI) developed previously, a disposable swab-in-capillary electrospray ionization (SC-ESI) source was designed in this study. With a micro medical swab for sampling and an integrated filter membrane for online filtration, SC-ESI was able to directly sample and MS analyze complex samples without the need for pretreatment. Coupled with a miniature mass spectrometer, SC-ESI was applied for direct analysis of effective ingredients in therapeutic drugs (in tablet, capsule, and liquid droplet) and drugs in saliva and quantitation of therapeutic drugs in blood. The limits of detection in absolute amounts were obtained as 1 ng for fentanyl and 0.5 ng for cocaine in saliva. Combining with an internal standard method, SC-ESI acquired linear quantitation ranges of 100-5000 ng/mL for imatinib in whole blood and 100-2000 ng/mL for clozapine in serum with high accuracies and precisions. The entire analysis process, from sampling to data acquisition, can be completed in less than 2 min. As demonstrated as a cheap, portable, and sampling-effective ionization source, SC-ESI has shown great potential for in situ drug analysis, especially in border drug screening and clinical therapeutic drug monitoring.